Title of Invention

SOMATOSTATIN OR BOMBESIN ANALOGS CONJUGATE

Abstract

The present invention relates to peptide agents that are analogs of biologically active peptides such as somatostatin and bombesin. The compounds of the invention have the general formula X- Y -Z-Q, where X is a cytotoxic agent, therapeutic agent, detectable label or chelating group, and Q is a biologically active peptide. In peptide agents of the invention Y is optionally a hydrophilic polymer or peptide, and Z is a linking peptide bonded to Q at the amino terminus of Q; having two, three, four, or five, amino acid residues selected to link X to Q, while retaining the biological activity of Q. Methods of using these peptide agents in the diagnosis and treatment of diseases are also disclosed.

Full Text

DIAGNOSTIC OR THERAPEUTIC SOMATOSTATIN OR BOMBESIN ANALOG CONJUGATES ANT) USES THEREOF Field of the Invention The invention relates to somatostatin and bombesin analogs and uses thereof for targeting compounds useful in the detection., diagnosis or treatment of disease. Backgi'ound The toxic side effects of many therapies^ including standard treatments for cancers, effectively limit the amount of agent that may be administered to a patient. Additionally, many agents cause organ-specific toxicities, further limiting the dose that may be delivered to the target tissue. For instance, the cardiotoxicity of many anthracycline family members reduces the maximum therapeutic dose available for this group of chemotherapeutic agents. Targeted dmg delivery of various detectable or therapeutic agents can lower toxicity in nomial tissue and increase the efficacy of t*eatment by allowing concentrated localized effects on specific tissues. Somatostatin, bombesin, or other biologically active peptide analogs have been used to detect tumor cells over expressing receptors specific for the peptides (see for example Denzler and Reubi, Cancer 85(1):188-198, 1999). Somatostatin, bombesin, and many other biologically active peptide agonist analogs are rapidly internalized after binding to their receptors (Luldnius et al, Acta One, 38:383-387, 1999; UOTQ\ Biochem, Pharmacol 47(l):63-76, 1994). This internalization of the peptide analogs may result in translocation to the cell nucleus (Chen et al, Am, J. Physiol Renal Physiol 279:F440-F448, 2000; Homick et al., J. Nucl Med, 41(7):1256-1263, 2000; Janson et al, J. Nucl MeJ. 41(9):1514-1518,2000). Somatostatin analogs bind particular somatostatin receptor subtypes that are present on the surface of specific nomial or diseased tissues. Somatostatin receptors are up-regulated in specific diseased tissues including inflammatory bowel diseases, rheumatoid arthritis, a variety of tumor types, and blood vessels supplying many tumors, often in a subtype-specific mamier. (Denzler -and Reubi, Cancer, 85:188-198, 1999; PlonoM^sld et al, Cancer Res. 60(11):2996-3001, 2000; Kahan et d\,Jnt J. Cancer S2(4):592-598, 1999; Gulec et al., Surg. Res. 97(2):131-137, 2001). Similarly, receptors specific for another biologically active peptide, substance P, can be up-regulated in various diseases (Id.). Somatostatin-related urotensin II peptide receptors have been found to be expressed on a number of neural tumors (Takahashi et al., Peptides 22:1175-1179, 2001). Receptors for GnRH II ligands/analogs have been located on many peripheral tissues of interest including breast, prostate, and the GI tract (Neill et ah, Biochem. Biophys. Res. Commun. 282:1012-1019; Millar et al, Proc. Natl. Acad. Set USA 98:963609641, 2001). At least five somatostatin receptors subtj^es have been characterized, and rumors can express various receptor subtypes (Shaer et al., Int. J. Cancer 70:530-537, 1997). Naturally occurring somatostatin and its analogs exliibit differential binding to these receptor subtypes, allowing precise targeting of a peptide analog to specific diseased tissues. The physical and chemical properties of many compounds such as c}4otoxic agents make their conjugation to biologically active peptides problematic. The agent or drug may reduce the specificits^ of binding or the biological activity of the peptide analog, limiting its effectiveness as a targeting agent. Additionally, therapeutic and cytotoxic agents may have chemical properties that cause reduced solubility and promote accumulation of drug-peptide analogs in certain organs, thus increasing toxicity and reducing efficacy. Effective means are needed to link cytotoxic agents to a targeting agent such as somatostatin, bombesin, or another biologically active peptide and to decrease non-target uptake of the cytotoxic agents, while retaining the activity of each component, thus maximizing therapeutic effects and minimizing toxicity. Furthennore, while iodinization and astatination (see Vaidyanathan et al, Nucl Med. Biol 27(4):329-337, 2000) hold great promise for use in imaging and possibly in aiding freatment of diseases associated with increased expression of a factor specific for a biologically active peptide, problems exist with the methods now available for labeling a range of peptide analogs. The use of labeled biologically active peptides has been studied in various systems. Radioactive halogens such as iodine have great potential as tumor imaging and cytotoxic agents. Promising isotopes mclude "I (K.S. Sastiy, Am. Assoc. Phys. Med. 19:1361-1370, 1992; Mariano, J. Nucl. Med. 41(9):1519-1521, 2000), ^^^I (Wheldon et ah, Radiother. Oncol, 21:91-99, 1991), ^^^1 (Blower et al., Eur, J. Nucl Med. 25:101-108, 1998; Janson et al, /. Nuc. Med 41(9):1514-1518, 2000; Mariani et al 1 Nuc. Med 41(9):1519-1521, 2000), and ^'"^I (Glaser et al., J. Labelled Compd. Radiopharm. 44(6):465-4S0, 2001). There are several problems associated with the addition of radioactive iodine atoms to peptides (Bakker et al., Eur. J. Nucl Med 23(7):775-781, 1996). One is the rapid loss of iodines from L-Tyr residues by specific de-iodination enzymes (Kawai et al., Nucl Med. Biol 17(4):369-76, 1990). Another problem is the gi'eat increase in hydrophobicity produced by addition of iodine to a peptide agent, which is associated with increased accumulation of radioactivity in the liver, interfering with tumor imaging and promoting severe toxicity. A further problem is loss of binding affinity when tyrosines next to the pharmacophore are iodinated. A linlcer capable of facilitating labeling of a variety of biologically active peptides without deleterious in vivo accumulation is needed. Summary of Invention I I - ^r - - .11 The present invention features biologically active peptides such as somatostatin or bombesin conjugated to chemical compounds through linkers that allow retention of the peptide's biological activity. Such peptide agents are useful for specifically targeting therapeutic agents, cytotoxic agents, or detectable labels to cells, such as cancer cells expressing somatostatin or bombesin receptors. In a first aspect, the invention features a peptide agent of the formula: X-Y-Z-Q wherein X is optionally selected from cytotoxic agents^ therapeutic agents, detectable labels or chelating gi'oups; Y is a peptide that increases the biodistribution of the peptide agent, a hydrophilic pohmier that includes a linlcer for X, or is omitted; Q is a biologically active peptide such as somatostatin or bombesin, and Z is a linldng peptide that, when bonded to Q at the N-temiinus or at a compatible side-chain amino gi'oup of Q, preserv^es at least 50% of the biological activity of Q. Z has the formula: A-B-C-E-F, where A is D-Lys, D-Tyi-, D-Ser, or L-Ser, or deleted; B is D-Lys or D-Tyr, or is deleted; C is Lys, Ser, hSer, Thr, Nle, Abu, Nva, (2,3, or 4) 3-pyridyI-AIa (Pal), Om, Dab, Dap, 4-NH.-Phe, D-4-OH-Pro, or L-4-OH-Pro, or .is deleted; E is D-Lys, D-Tyr, D-Ser, D-4-OH-Pro, L-4-OH-Pro, S-iodo-D-Tyi', 3-5 diido-D-Tyr, 3-astatine-D-Tyr, 3-5 astatine-D-Tyr, 3-bromo-D-Tyr, 3-5 dibromo-D-TyT, D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Gln; and F is D-Lys, D-Tyr, D-Ser, L-Ser, D-4-OH-PTO, L-4-OH-Pro, 3-iodo-D-Tyi\ 3-5 diido-D-Tyr, 3-astatine-D-Tyr, 3-5 astatine-D-Tyi\ 3-bromo-D-Tyi', 3-5 dibromo-D-Tyr, D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Gin; provided that when A, B, C, and E are Tyr, Tw, Lys, and Tyr, respectively, F is not Lys; and when A, B, C, and E, are Lys, Tyr, Lys, and Tyr, respectively, E is not Tyi* or Lys; and when A and B are deleted, and C and E are Lys and Tyr, respectively, F is not Tyr or Lys. In a second, related aspect, the invention features a peptide agent having the formula: X-Y-Z-Q wherein: X is a cytotoxic or therapeutic agent; Y is a peptide that increases the hydrophilic distribution of the peptide agent, a hydrophilic polymer that includes a linker for X, or is omitted; Q is a peptide having biological activity; and Z is a linlcing peptide that when bonded to Q at the N-terminus or at a compatible side-chain amino group of Q, presences at least 50% of the biological activity of Q, wherein Z has the fomiula: A-B-C-E-F where A is D-Lys, D-Tyr, D-Ser, or L-Ser, or is deleted; B is D-Lys or D-Tyr, or is deleted; C is Lys, Ser, hSer, Thr. Nle. AbU; Nva, (2, 3, or 4) 3-pyridyl-AIa (Pal), Ora, Dab, Dap, 4-NH2-Phe, D-4-OH-Pro, or L-4-OH-Pro, or is deleted; E is D-Lys, D-T}T, D-Ser, D-4-OH-Pro, L-4'OH-Pro, 3-iodo-D-Tyi-, 3-5 diiodo-D-T}a-, 3-astatine-D-Tyr, 3-5 astatine-D-Tyr, 3-bromo-D-Tyi*, 3-5 dibromo-D-Tyr, D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Gln; and F is D-Lys, D-Tyr, D-Ser, L^Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyi\ 3-5 diiodo-D-Tyr, 3-astatine-D-Tyr, 3-5 astatine-D-Tyr, S-bromo-D-Tyr, 3-5 dibromo-D-Tyi', D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Gin; provided that when A, B, C, and E are Tyr, Tyr, Lys, and Tyr, respectively, F is not Lys; and when A, B, C, and E are Lys, Tyr, Lys, and Tyr, respectively, E is not Tyi- or Lys; and when A and B are deleted, and C and E are Lys and Tyi', respectively, F is not Tyr or Lys. The Z peptide linker may thus be 2, 3, 4, or 5 residues in length. In one embodiment of the first and second aspects of the invention, X is a cytotoxic agent or cytotoxic agents. Preferably, X is an antinietabolic agent. The cytotoxic agent may be selected from the group consisting of doxorubicin, methotrexate, camptothecin, homocamptothecins, rhizoxins, dolistatins, paclitaxel, combretastatin, and maytansinoids, or derivatives or analogs thereof. For example, the cytotoxic agent methotrexate may be linked thi'ough the liM:er Z or Y-Z to a peptide analog, forming a peptide agent of the invention. Preferred cytotoxic agents are rhizoxin, rhizoxin-D, caniptothecin and its active analogs, homocamptothecin, ansamitocin P-3, dolistatins, epothilones, combretastatins, and combretastatin A-4. In other prefen*ed embodiments, the linldng peptide Z is D-Ser-Nle-D-Ser-D-Ser, D-Ser-Lys-D-Ser-D-Ser, D-Ser-Lys-D-Tyr-D-Tyi', D-Ser-Lys-D-T\T-D"Ser, D-Ser-Ser-D-Lys-D-Ser, D-Ser~Ser-D-Lys-Ser, D-Ser-Nle-D-Tyi'-D-Ser, D-Ser-Pal-D-Tyi'-D-Ser, D-Ser-Tlii*-D-Tyr-D-Ser, Lys-D-Ser-D-Ser, Ser-D-Lys-D-Ser, Ser-D-Lys-Ser, N]e-D-Tyr-D-Ser,Lys-D-Tyr-D-Ser, Pal-D-LyS"D^Ser, Tln'-D-Tyr^D-Ser, D-Ser-D-Lys_, D-Ser-D-Tyr, D-Lys-D-Lys, D-Lys-D-Tyr, or D-Tyr-D-Lys. In a third aspect of the invention, the peptide agent has the formula: X-Y-Z-Q, where X is a chelating group, or is omitted; Y is a peptide that increases the hydrophilic biodistribution of the peptide agent, a hydrophilic polymer that includes a linlcer for X, or is omitted; Q is a peptide having biological activity; Z is a linldng peptide that, when bonded to Q at the N-temiinus or at a compatible side-chain airdno CToup of Q, preseives at least 50% of the biological activity of Q. In this aspect of the invention, Z has the fomiula: C-E-F, where C is Lys, Om, Dab, Dap, 4- NHs-Phe, Nle, Ser, hSer, Abu, Nva, D-4-OH-Pro, or L-4-OH-Pro, or is deleted; and E and F are each independently selected from the group consisting of: D-Lys, D-Tyr, D-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyr, 3-5 diiodo-D-T>T, 3-bromo-D-Tyr, 3-5 dibromo-D-Tyr, D-Asn, D-Asp, L-Asp, D-Glu, or L-Glu; and when C and E are Lys and D-Tyr, respectively, F is not D-T)T or D-Lys. In altemative embodiments of the third aspect, the peptide agents of the invenrion are attached to a detectable label directly or indirectly. The detectable label is prefei'ably radioactive, such as radiolabeled iodine, astatine, or bromine bonded to an amino acid residue of the agent. Alternatively, X may be a chelating group and may contain, for example, an isotope of Lu, In, Y, or Sm, or X may be omitted. If X is omitted, Y may be lower acetylated, snccinylated, maleinylated or fumarylated. In multiple embodiments of the third aspect, the invention features a peptide agent in which Z is: Lys-D-Tyr-D^Ser, Lys-D^Ser-D-Ser, or Nle-D-Tyr-D-Ser. In another embodiment of the third aspect of the invention, Z may be tliree amino acids in length. Z is preferably the peptide agent of the formula:. where C is selected from the amino acids listed as above, E is D-Tyi' and F is D-Ser. Alternatively, Z maybe Lys-D-Tyr-D-Ser, Lys-D-Ser-D-Ser, orNle-D-Tyr^D"Ser. In another embodiment of the third aspect, the invention features compositions in which Z has the fomiula: C-E-F where C is selected from the group consisting of Lys, Om, Dab, Dap, 4-NH2-Phe, Nle, Ser, hSer, Abu, Nva, D^4-OH-Pro, and L-4-OH-Pro, or is deleted; E is D-Tyr; and F is D-Ser. In the first, second, and third aspects of the invention, Y may be a peptide sequence that increases the hydrophilic biodistribution of the biologically active peptide conjugate. For example, in a preferred embodiment, Y IS of the formula U(V-V)n, wherein U is D-Pro, L-Pro, D-4-OH-Pro, L-4-OH-Pro, Sarcosine, Lys, Om, Dab, Dap, 4-NH2-Phe, or (NH.-CCHaVCOOH), where m==2-10, inclusive, or is deleted; each V is independently selected from the group consisting of: D-Ser, L-Ser, D-Thr, L-Thr, D-Gln, L-Gln, D-Asn, L-Asn, D-4-OH-Pro, or L-4 hydroxy-Pro; and n=^l-50, inclusive. In another preferred embodiment, each V is independently D-Ser or L-Ser. In another preferred embodiment, at least one V is a D-amino acid. In the alternative, Y may be a hydrophilic polymer. For example, Y may be polyethylene glycol, polyvinyl acetate, polyvinyl alcohol, HPMA (N- (2-hydroxypropyl) methacrylamide) orHPMA copolymers, a, p-poly(N-hydroxyethy])-DL-aspartamide (PHEA), a, (3-poly(N-hydroxypropyl)-DL-aspartamide, or polyvinyl acetate. The biologically active peptide Q is preferably a somatostatin peptide or a bombesin peptide. In one embodiment of the invention, Q is bombesin and Z has the fonnula: E-F where E is D-Lys,, D-Tyi\ D-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyr, 3-5 diiodo-D-Tyi\ 3-astatine-D-Tyr, 3-5 astatine-D-T>a\ 3-bromo-D-Tyr, 3-5 dibromo-D-Tyi*, D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Gln; and F is D-Lys, D-Tyr, D-Ser, L-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyi', 3-5 diiodo-D-Tyr, 3-astatine-D-Tyr, 3-5 astatine-D-Tyr, 3-bromo-D-Tyr, 3-5 dibromo-D-Tyr, D-Asn, L-Asn, D-Asp, L-Asp, D-Gln, L-Glu, D-Gln, orL-Gln. The present invention also provides methods of n^eating or diagnosing a disease comprising administering to a subject suffering from said disease a therapeutically effective amount of the peptide agents of the invention. For example tumors, or their angiogenic vessels, of the lung, breast, brain, eye, prostate, or colon, the corresponding angiogenic blood vessels, ortimaors of neuroendocrine origin, for example carcinoid syndrome, may be treated with a peptide agent. Other features and advantages of the invention will be apparent from the following detailed description and from the claims. Definitions In accordance with the present invention, by "therapeutic agenf is meant any compound that is used in the detection, diagnosis or treatment of human disease. Such compounds may be naturally occurring, modified, or synthetic. Therapeutic agents may promote or inhibit any biological process implicated in a human disease pathway. Preferred disease targets include, but are not limited to, inflammatory bowel disease, rheumatoid arthritis, neoplastic cells or aberrantly proliferating cells, carcinoid syndrome, acromegaly, and angiogenesis. A therapeutic agent may be, for example, antineoplastic, including cytotoxic. Antineoplastic agents maybe alkylating agents, antibiotics, antimetabolites, hoiTnonal agonists or antagonists, tubulin inhibitors, topoisomerase I and II inhibitors, or immunoraodulators. They may operate through other mechanistic pathways, or antineoplastic agents may be supplementary potentiating agents. By "cytotoxic agent" is meant any naturally occurring, modified, or synthetic compound that is toxic to tumor cells. Such agents are useful in the ti'eatment of neoplasms, as well as inflammatoiy diseases, autoimmune disorders, and in the ti-eatment of other symptoms or diseases characterized by cell proliferation or a hyperactive cell population. Cytotoxic agents include, but are not limited to, alkylating agents, antibiotics, antimetabolites, tubulin inhibitors, topoisomerase 1 and II inhibitors, hormonal agonists or antagonists, or immunomodulators. They may also be cytotoxic when activated by light or infi-ared (Photofrin, IR dyes; A^ar. Biotechnol 19(4):327-331, 2001). They may operate through other mechanistic pathways, or c\toxic agents may also be supplementary potentiating agents. By "detectable label" is meant any type of label which, when attached to a peptide agent, renders the compound detectable. A detectable label may be toxic or non-toxic, and may have one or more of the following attiibutes, without restriction: fluorescence (Kiefer et ah, WO 9740055), color, toxicity (e.g., radioactivity, e.g., a y-emitting radionuclide. Auger-emitting radionuclide, p-emitting radionuclide, an a-emitting radionuchde, or a positron-emitting radionuclide), radiosensitivity, or photosensitivit\\ Although a detectable label may be directly attached to an amino acid residue of an analog of the invention, a detectable label may also be indirectly attached, for example, by being complexed with a chelating gi*oup that is attached (e.g., linked via a covalent bond or indirectly linked) to an amino acid residue of an analog. A detectable label may also be indirectly attached to an analog by the ability of the label to be specifically bound by a second molecule. One example of this t}^e of an indirectly attached label is a biotin label that can be specifically bound by the second molecule, streptavidin. The second molecule may also be linlced to a ■ moiety that allows neutron capture (e.g., a boron cage as described in, for example, Kahl et al, Proc. NatL Acad. Sci USA 87:7265-7269,1990). A detectable label may also be a metal ion from heavy elements or rare earth ions, such as Gd ', Fe ', Mn , or Cr"^ (see, for example. Invest Radiol: 33(10):752-761, 1998). Preferred radioactive detectable labels are radioactive iodine labels (e.g., '"I, L ^ I, " 1, or I) that are capable of being coupled to each D- or L-Tyi' or D- or L-4-amino-Phe residue present in the analogs of the invention. Preferred non-radioactive detectable labels are the many loiown dyes that are capable of being coupled to NH2-terminal amino acid residues. Prefen-ed examples of detectable labels that may be toxic to cells include l'?2 P3 124 125 ricin. diptheria toxin, and radioactive detectable labels (e.g., "I, "I, L I, 13U ]77T 64^ 61 r^ 153^^ \66-.j 186-^ 188-n 21] . 212^^. 225. 67^ L Lu, Cu, Cu, Sm, Ho, Re, Re, At, Bi, Ac, Ga, 68^ 75-n 76^^ 77-p, 117mc 47o 109^.-, ^9^. 159^, 149^ 142-^, UK Ga, Br, Br, Br, Sn, Sc, Pd, Sr, Gd, Pm, Pr, Ag, 165T^ 213^. 111. IMm. 201^. 195mT.. 193-^,^ 86., j 90^;-. ^, , Dy, Bi, In, In, Ti, Pt, Pt, Y and Y). These compounds, and others described herein may be directly or indirectly attached to a biologically active peptide or its analogs. A toxic detectable label may also be a chemotherapeutic agent (e.g., camptothecins, homocamptothecins, 5-fluorouracil or adriamycin), or may be a radiosensitizing agent (e.g., Taxol, gemcitabine, fluoropyrimidine, metronitozil, or the deoxycytidine analog 2',2' difluoro- 2'-deoxycytidine (dFdCyd) to which is directly or indirectly attached a somatostatin analog of the present invention. By 'chelating group" is meant any group covalently bound to the peptide agent, that may complex with a detectable label, such as a metal, photosensitizing agent, etc. Chelating groups, for example, include an iminodicarboxylic group or a polyaminopolycarboxylic group. Chelating gi'oups may be attached to a peptide agent of the invention using the methods generally described in Liu et al.^ Bioconjiigate Chem. 12(4):653, 2001; Alter et al, U.S.P.N. 5,753,627; and PCT Publication No. WO 91/01144; both of which are hereby incoiporated by reference). An analog of the invention may be complexed, tb'ough its attached chelating agent, to a detectable label, thereby resulting in an analog that is indirectly labeled. Similarly, cytotoxic or therapeutic agents, may also be attached via a chelating gi'oup to a peptide agent of the invention. By "biologically active peptide" is meant any namrally occuning, modified, or synthetic peptide that is involved in a biological process or function. Examples of biologically active peptides include, but are not limited to: honnones, growth factors, neurotransmitters, antigens, antibodies, or fragments thereof, etc. By "peptide" is meant any polypeptide, peptide (including cyclic or branched peptides), or protein comprising two or more amino acids joined to each other by peptide bonds or modified peptide bonds. "Peptide" refers to both short chains, commonly refen-ed to as peptides, oligopeptides, or ohgomers, and to longer chains, up to about 100 residues in length. Peptides may contain amino acids other than the 20 gene-encoded amino acids, and linkages other than peptide bonds. "Peptides" include amino acid sequences modified either by natural processes, or by chemical modification techniques which are well known in the art. Modifications may occur anywhere in a pol}^eptide, including the peptide backbone, the amino acid side-chains, and the amino or carboxyl termini. The notations used herein for the peptide amino acid residues are those abbreviations conrmonly used in the art. The less common abbreviations Abu, Ava, p-Ala, hSer, NIe, Nva, Pal, Sar, Dab, and Dap stand for 2-amino-but}'Tic acid, amino valeric acid, beta-aminopropionic acid, homoserine, norleucine, norvaline, (2,3, or 4) 3-pyridyl-Ala, 1,4-diaminobutyric acid, sarcosine, and 1,3-diaminopropionic acid, respectively. In all aspects of the invention, it is »• noted that when amino acids are not designated as either D- or L-amino acids, the amino acid is either an L-amino acid or could be either a D- or L-amino acid. By 'analog" is meant a molecule that differs &om, but is structurally, functionally, and/or chemically related to the reference molecule. The analog -may retain the essentia] properties, functions, or structures of the reference molecule. Most preferably, the analog retains at least one biological function of the reference molecule. Generally, differences are limited so that the structure or sequence of the reference molecule and the analog are similar overall. A peptide analog and its reference peptide may differ in amino acid sequence by one or more substitutions, additions, and/or deletions, in any combination. A substituted or inserted amino acid residue may or may not be one encoded by the genetic code. An analog of a peptide or pol)'peptide may be naturally occuning such as an allelic variant, or it may be a variant that is not Icnown to occur naturally. Non-naturally occurring analogs of peptides may be made by direct synthesis, by modification; or by mutagenesis techniques. By "somatostatin peptide" is meant a somatostatin analog having at least one biological activity of native somatostatin; preferably, this activity is the ability to specifically bind to a somatostatin receptor on a somatostatin receptor-bearing cell. Many such analogs having biological activity are loiown and have been described, for example, in Homik et al, U.S.P.N, 5,770,687; Coy et a!., U.S.P.N. 5,708,135; Hoeger ei al, U.S.P.N. 5,750,499; McBride et ai, U.S.P.N. 5,620,675; Coy et al, U.S.P.N. 5,633,263; Coy et al, U.S.P.N. 5,597,894; Taylor et ai, U.S.P.N. 5,073,541; Coy et al, U.S.P.N. 4,904,642; Dean, U.S.P.N. 6,017,509; Hoffman et ah, WO 98/47524; and A. E. Bogden, U.S.P.N. 5,411,943, each of which is hereby incorporated by reference. The tenn "bombesin peptide" encompasses bombesin peptide analogs having at least one biological activity of native bombesin; preferably, this activity is the ability to specifically bind to one or all of the three Icnown bombesin receptor subtypes on a bombesin receptor-bearing cell. Bombesin analogs include, "but are not liinited to, peptides selected from the group containing the octapeptide G-Trp-H-I-His-J-K-NHV, wherein G is Gin, Asn, Nle, or Nva; H is Ava, Gly, Leu, Val, He, Me, or Nva; I is p-Ala, 4-aminobutyi-ic acid, Gly, Ala, D-Ala, N-Me-Ala, or N-Me-D-Ala; J is Phe, Tyr, 4-Cloro-Phe, 4-Fluoro-Phe, 4-Bromo-Phe, 4-N02-Phe, Ala, Gly, Leu, Val, Ile^, Nle, or Nva; K is Met, Phe, Tyr, 4-Cloro-Phe, 4-Fluoro-Phe, 4-Bromo-Phe, 4-N02-Phe, Ala, Gly, Leu, Val, He, Nle, or Nva; and N represents an amide or a N-alkylamide and V is H or a lower alkylamide. By "alkyl" is meant an aliphatic branched or straight chain hydrocarbon group. An alkyl is optionally substituted with one or more substituents which may be the same or different. By "lower alkyl" is meant a branched or st'aight chain alkyl gi'oup having less than 11 carbon atoms, preferably a CpCs alkyl. By 'lower alkylamide" is meant a lower alkyl group as described above substituted with one or more amide^containing groups. By "hydrophilic biodistribution" is meant the affmity of the peptide agents of the invention for the bodily fluids of a subject administered the peptide agents (e.g., blood, cerebrospinal fluid, urine, or other bodily fluids), such that the peptide agents distribute tluoughout the body of the subject, but are rapidly secreted in the urine via the kidney, while avoiding uptake by peripheral organs such as liver, gall bladder, and Icidney proximal tubules. By "hydrophilic polymer" is meant a naturally occuning or synthetic water-soluble polymer optionally modified that alters the biodisti*ibution of a peptide agent of the invention. Examples of such polymers include, but are not limited to poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), dextran, hydroxyelthyl starch, gelatin, PVP, PHPMA, poly a, {3[N(2-hydroxyeth34)D,L aspartamide (PHEA), polysuccinamide (PSI), etc. These polymers may be modified by, for example, succinylation (negative charge), partial hydrolysis of PSI (carboxylic groups), or reaction with compounds to add amino- or carboxyl- containing groups, etc. Such optional modifications may increase or change the polymer's hydrophilicity or enable coupling to the peptide or cytotoxic, therapeutic, or chelating segments of a peptide^agent of the invention. Such polymers and modifications are known in the art and are described in, for example, Yamoaka et al, J. Pharmacol Set 83:601-606, 1994; Rypacek et al., Pflugers Arch. 392:211-217, 1982; Yamoaka et al., J. Pharm. Pharmacol. 47:479-486, 1995, Francesco, Bioconjugate Chemistiy ■ 9(4):41S-450, 199S, Duncan and Spreafico, CUn. Pharmacoldnet. 27(4):290-306, 1994, which are hereby incorporated by reference. Other features and advantages of the invention will be apparent from the following detailed description thereof, and from the claims. Brief Description of the Drawings FIG 1. is a gi-aph showing the inhibitory effects of a typical methotrexate-somatostatin conjugate on proliferation of neuroblastoma IMR-32 cells compared to non-conjugated methotrexate and non-conjugated somatostatin analog segment. The equivalent potencies of methotrexate-peptide conjugate and methotrexate alone in this in vitro system are readily apparent. Control peptide JF-08-89 is D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-Nle-D-Tyr-D-Ser-cyclo[Cys-Phe-D-Trp-Lys-Tlir-Cys]^Thi--NH2 (SEQ ID NO: 10). FIG. 2. is a graph displaying the biodistribution of hydrophilic peptide a^enls of the invention. Two " I-labeled, hydrophihc somatostatin analogs are depicted. Note the lack of accumulation of radioactivity in normal tissue including liver, and the rapid and high efficiency elimination of the labeled peptide agents in urine and feces. Peptide JF-08-73 is ^"^I-succinoyl-D-Asp-D-Ser-D-Ser-D-Ser^D-Ser-D-Ser-D-Asp-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-Lys- D-TvT-D-Tyr-cyclo[Cys-Phe-D-Tip-Lys-Tlir-Cys]-Thr-NTl2 (SEQ ID NO: 11). Peptide JF-08-53 is ^^'I-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Lys-D-Tyi--D-Ser- cycIo[Cys-Phe-D-Trp-Lys-Thi--Cys]-Thi'-NH2 (SEQ ID NO: 12). Detailed Description A family of peptide agents has been developed that utilizes a novel, universal linking sequence. The linking sequence enables conjugation of therapeutic agents^ cytotoxic agents, chelating groups, or detectable labels to biologically active peptides without substantial loss of biological potency of the targeting segment of the peptide agent. These peptide agents or analogs may additionally include a hydrophilic biodistribution enhancing segment in another aspect of the invention, increasing potency of treatment by targeting the analogs away from the liver towards rapid elimination via the kidney. A peptide agent of the invention is of the general fomiula: X-Y-Z^Q (FoiTOula I) wherein X is optionally selected from cytotoxic agents, a therapeutic agents, detectable labels or chelating groups; Y is an hydrophihc element; Q is a biologically active peptide such as somatostatin or bombesin, and Z is a linlcing peptide that, when bonded to Q at the N-teraiinus or to a compatible side-chain amino gi'oup of Q, presences at least 50% of the biological activity of Q. An example of a substitution of Q is position 6 of the GnRH peptides. This position is very tolerant of substitution of, for instance, D-Lys, the epsilon amino gi'oup of which could be used for the described attachment of cytotoxic or radioactive groups with retention of receptor affmit}^ Z has the formula; A-B-C-E-F where A is D-Lys, D-Tyi', D-Ser, or L-Ser, or is deleted; B is D-Lys or D-T)T, or deleted; C is Lys, Ser, hSer, Nle, Abu, Nva, (2,3, or 4) 3-p}a*idy]-Ala 9 (Pal), Om, Dab, Dap, 4-NH2-Phe, D-4-OH-Pro, or L-4-OH-Pro, or is deleted; E is D-Lys, D-Tyi\ D-Ser, D-OH-Pro, L-4-OH-Pro, D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Ghi; and F is D-Lys, D-Tyr, D-Ser, D-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyr, 3-5 diido-D-Tyi-, 3-astatine-D-Tyi% 3-5 astatine-D-Tyr, 3-bromo-D-Tyr, 3-5 dibromo-D-Tyr, D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Gln; provided that when A, B, C, and E are Tyr, Tyi*, Lys, and Tyr, respecitively, F is not Lys; and when A, B, C, and E are Lys, Tyi", Lys, and Tyi\ respectively, E is not Tyr or Lys; and when A and B are deleted, and C and E are Lys and Tyr, respectively, F is not Tyi* or Lys. The Z peptide linker may thus be 2, 3, 4, or 5 residues in length. Included among the peptide agents synthesized thus far are the followins: .TF-07-100 MTXCOO-CHoCO-D-Lys-D-Tyr-Lys-D-Tyr-D-Lys-Cys-Phe-D-Trp-Lys-Thr-Cys-Tlir-NH2 (SEQIDNO:!) JF-08-87A MTXCOO-CH2CO-(D-Ser)5-Lys-D-Tyi--D-Tyi--Cys-Phe-D-Trp-Lys-Tlii--Cys-Thi--NH2 (SEQ ID NO: 2) JF-09-35 MTXC00NH-Leu-A]a-Leu-Ala-(D-Ser)5-Lys-D-Tyr-D-Ser-Cys-Phe-D-Tip-Lys-Tlu--Cys-Thi--NH2 (SEQ ID NO: 3) MTXCOO-CH2CO-(D-Ser)5-Lys-D-Tyi--D-Tyr-cyclo[Cys-Phe-D-Trp-Lys-Thr-Cys]-Thr-NH2 (SEQ ID NO: 4) MTXCOO-CH2CO-(D-Ser-Ser)4-Tyr-D-Ser-Gln-Trp-Ala-Val-p-A]a-His-Phe-Nle -NH2 (SEQ ID NO: 5) JF-09-73 Thiocolchicine-thioether-Lys-(D-Ser)io-NIe-D-Tyr-D-Ser-cyclo[Cys-Phe-D-Trp-Lys-Tlii--Cys]-Tlii--NH2 (SEQ ID NO: 6) JF-09-93 Camptothecm-carbonyl-SaT-D-Ser-Nle-D-Tyr-D-Ser-cyclo[Cys-Phe-D-Trp-Lys-Tlir-Cys]-Thi--NH2 (SEQ ID NO: 7) JF-09-95 Camptothecin-carbonyl-Pro-D-Ser-Nle-D-Tyr-D-Ser-cyclo[Cys-Phe-D-Trp-Lys-Thr-Cys]-Thr- NH2 (SEQ ID NO: 8) JF-09-99 Camptothecm"Carbonyl-Hydroxyprolme-D-Ser-Nle-D-Tyr-D-Ser-cyclo[Cys-Phe-D-Trp-Lys-Tlii--Cys]-Thr- NH2 (SEQ ID NO: 9) Additional sequences of peptide agents of the invention are found in Table 1. The present invention circumvents the accumulation of toxic peptide analog in tissues, through inclusion of both the Z linker^ containing hydrophilic resides, and optional inclusion of an elongated hydrophilic linlcer. These linkers promote rapid elimination of intact, non-bound peptide agents tlirough the kidneys. Polyethylene glycol (PEG), a, p-poly(N-hydroxyethyl)-DL-aspartamide (PHEA), and polyvinylalcohol (PVA) gi-oups contained in this invention are also Icnown to be excellent promoters of rapid renal secretion which is correlated generally with lower potential drug toxicities (Yamoaka et al, J. Pharmacol Scl, 83:601-606, 1994; Rypacek et al, PflugersArcL, 392:211-217, 1982; Yamoaka et al, J. Phaim. Pharmacol, 47:479-486, 1995). We posit that these groups also promote lowered toxicity emanating from bioavailable, non-interaalized conjugates. The peptide agents of the invention include a universal linldng sequence designed to presence full biological potency of the peptide analogs when conjugated to a cytotoxic agent. A peptide analog of the invention has a biological potency that is preferably greater than or equal to the parent peptide analog from which it is derived, with a specificity that is greater, lesser, or equivalent to the parent peptide's target specificity. For example, a somatostatin analog may bind to more somatostatin receptor subtypes than naturally occurring somatostatin, or it may bind to a particular receptor subtype. Some analogs of the invention contain D-isomers of amino acids or analogs thereof, facilitating stable coupling of cytotoxic agents while retaining high receptor affmity and biological potency of the peptide analog. Preferably a cytotoxic agent will be coupled via a linkage likely to encourage release of free cytotoxic agent intracellularly. Additionally, because the somatostatin analogs of the invention are ^'ariously hydrophilic, they are water-soluble and, thus, have enlianced use as compared to previous hydrophobic analogs. The hydrophilic analogs described herein are soluble in blood, cerebrospinal fluid, and other bodily fluids, as well as in urine, facilitating excretion by the Icidneys. This hydrophilic character facilitates the delivery of the analogs of the invention to almost every area of the body. The invention also discloses specific hydrophihc elements for incorporation into peptide analogs, allowing modulation of the analog's hydrophilicity to adjust for the chemical and structural nature of the various conjugated c}^otoxic agents. Somatostatin agonist analogs are rapidly internalized after binding to their receptors (see Lukinius et ah Acta One, 38:383-387. 1999) and can thus be used as vectors for targeting various therapeutic agents - such as traditional tumor cyctotoxic agents. It is possible that the specificity of such anti-timior agents can be drastically improved since many tumor types heavily overexpress somatostatin type 2 receptors. In this maimer, we propose that the toxic side effects associated with all conjugatable c^^otoxic agents can be usefully lowered as long as a potent hybrid molecule can be designed which retains very high affmity for somatostatin receptors. The invention features the use of a linking sequence, referred to as Z in formula I, which we have found enables many long N-teiToinal amino acid sequences and large molecules to be conjugated to the N-temiinus of the somatostatin analogs with full retention of agonist potency. This linldng sequence can be used to add longer, enzymatically stable (via use of D-amino acids), hydrophihc peptide sequences (the Y element of formula I) designed to tarset the resulting coniugates away from the liver towards rapid elimination via the Iddney. Alternatively, a hydrophilic polymer may be linked to the peptide analog via the Z linker. Tliis promotes lowered toxicity emanating from non-internalized conjugates. The peptide analog also includes an element, denoted as Y in foraiula I, which may be optimized to facilitate biodistribution of the particular peptide ' agent conjugated to a cytoxic or therapeutic group, or a chelating gi'oup or detectable label. The Y linlcer may be a peptide or a polymer such as PEG or PVA. If Y is a hydrophilic peptide, Y may be 1 to 50 amino acids in length, or more preferably 3 to 15 residues in length. For example, Y maybe 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, IS, 19 or20 amino acid residues in length. Wlien a peptide, Y may contain charged or non-polar amino acids, their analogs or derivatives that are naturally occun-ing, synthetic or modified. The linking sequences of the invention are used to conjugate a biologically active peptide refeired to as Q in formula I, to various therapeutic or diagnostic agents, referred to as X in formula I. The component X of fonnula I can be any known cytotoxic or therapeutic moiety, e.g., Antineoplastic agents such as: Acivicin; Aclambicin; Acodazole Hydrochloride; Acronine; Adozelesin; Adriamycin; Aldesleuldn; Alti'etamine; Ambomycin; A. metantrone Acetate; Aminoglutethimide; Amsacrine; Anastrozole; Anthramycin; Asparaginase; Asperlin; Azacitidine; Azetepa; Azotomycin; Batimastat; Benzodepa; Bicalutamide; Bisantrene Hydrochloride; Bisnafide Dimesylate; Bizelesin; Bleomycin Sulfate; Brequinar Sodium; Bropiiimine; Busulfan; Cactinomycin; Calusterone; Camptothecin; Caracemide; Carbetimer; Carboplatin; Carmustine; Cambicin Hydrochloride; Carzelesin; Cedefingol; Chlorambucil; Cirolemycin; Cisplatin; Cladribine; Combretestatin A-4; Crisnatol Mesylate; Cyclophosphamide; Cytarabine; Dacarbazine; DACA (N- [2- (Dimethyl-amino) ethyl] acridine-4-carboxamide); Dactinomycin; Daunorubicin Hydrochloride; Daunomycin; Decitabine; Dexomiaplatin; Dezaguanine; Dezaguanine Mesylate; Diaziquone; Docetaxel; Dolasatins; Doxorubicin; Doxorubicin Hydrochloride; Droloxifene; Droloxifene Citrate; Dromostanolone Propionate; Duazomycin; Edatrexate; Eflomithine HydrocUoride; Ellipticine; Elsamitrucin; Enloplatin; Enpromate; Epipropidine; Epimbicin Hydrochloride; Erbulozole; Esorubicin Hydrochloride; Estramustine: Estram"ustine Phosphate Sodium; Etanidazole; Ethiodized Oil 1131; Etoposide; Etoposide Phosphate; Etoprine; Fadrozole ' Hydrochloride; Fazarabine; Fenretinide; Floxuridine; Fludarabine Phosphate; Fluorouracil; 5-FdUMP; Flurocitabine; Fosquidone; Fostriecin Sodium; Gemcitabine; Gemcitabine Hydrochloride; Gold Au 198; Homocamptothecin; Hydrox}^rea; Idarabicin Hydrochloride; Ifosfamide; Ilmofosine; Interferon Alfa-2a; Interferon Alfa-2b; Interferon Alfa-nl; Interferon Alfa-n3; Interferon Beta-I a; Interferon Ganima-I b; Iproplatin; Irinotecan Hydrochloride; Lanreotide Acetate; Letrozole; Leuprolide Acetate; Liarozole Hydrochloride; Lometi'exol Sodium; Lomustine; Losoxanti'one Hydrochloride; Masoprocol; Maytansine; Meclilorethamine Hydrochloride; Megestrol Acetate; Melengesti-ol Acetate; Melphalan; Menogaril; Mercaptopurine; Methotrexate; Methotrexate Sodium; Metoprine; Meturedepa; Mitindomide; Mitocarcin; Mitocromin; Mitogillin; Mitomalcin; Mitomycin; Mitosper; Mitotane; Mitoxanti'one Hydrochloride; Mycophenolic Acid; Nocodazole; Nogalamycin;Ormaplatin; Oxisuran; Pachtaxel; Pegaspargase; Pehgmycin; Pentamustine; PeploycinSulfate; Perfosfamide; Pipobroman; Piposulfan; Ph'oxantrone Hydrochloride; Plicamycin; Plomestane; Porfimer Sodium; Poi*firomycin; Prednimustine; Procarbazine Hydrochloride; Puromycin; Puromycin Hydrochloride; Pyrazofurin; Rhizoxin; Rhizoxin D; Riboprine; Rogletimide; Safmgol; Safmgol Hydrochloride; Semustine; Simtrazene; Sparfosate Sodium; Sparsoraycin; Spirogermanium Hydrochloride; Spiromustine; Spiroplatin; Streptonigrin; Streptozocin; Strontium Chloride Sr 89; Sulofenur; Tahsomycin; Taxane; Taxoid; Tecogalan Sodium; Tegafor; Teloxantrone Hydrochloride; Tenioporfm; Teniposide; Teroxirone; Testolactone; Thiamiprine; Thioguanine; Thiotepa; Thymitaq; Tiazofurin; Tirapazamine; Tomudex; TOP53; Topotecan Hydrochloride; Toremifene -Citrate; Tresto]one Acetate; Triciribine Phosphate; Trimetrexate; Triraetrexate Glucuronate; Triptorelin; Tubulozole Hydrochloride; Uracil Mustard; Uredepa; Vapreotide; Verteporfin; Vinblastine; Vinblastine Sulfate; Vincristine; Vincristine Sulfate; Vindesine; Vindesine Sulfate; Vinepidine Sulfate; Vinglycinate Sulfate; Vinleurosine Sulfate; Vinorelbine Taitrate; Vinrosidine Sulfate; Vinzolidine Sulfate; Vorozole; Zeniplatin; Zinostatin; Zorubicin Hydrochloride; 2-Chlorodeoxyadenosine; 2' Deoxyformycin; 9-aminocamptothecin; raltitrexed; N-propargyl-5,S-dideazafolic acid; 2c}iIoro-2'-arabino-fluoro-2'-deoxyadenosine; 2-chloro-2'deoxyadenosine; anisomycin; tiichostatin A; hPRL-G129R; CEP-751; Unomide; sulfur mustard; nitrogen mustard (mechlor ethamine); cyclophosphamide; melphalan; chlorambucil; ifosfamide; busulfan; N-methyl-Nnitrosourea (MNU); N, N*-Bis (2-chloroethyl)-N-niti-osourea (BCNU); N- (2-chloroethyl)-N' cyclohexyl-K-nitrosourea (CCNU); N- (2-ch]oroethyl)-N'-" (trans-4-methylcyclohexyl'N-nitrosourea (MeCCNU); N- (2-chloroethyl)-N'- (diethyl) ethylphosphonate-N-niti'osourea (fotemustine); streptozotocin; diacarbazine (DTIC); mitozolomide; temozolomide; thiotepa; mitomycin C; AZQ; adozelesin; Cisplatin; Carboplatin; Ommplatin; Oxaliplatin;Cl-973; DWA2114R; JM216; JM335; Bis (platinum); tomudex; azacitidine; cytarabine; gemcitabine; 6- >. Mercaptopurine; 6'Thioguanine; H^^oxanthine; teniposide 9-amino camptothecin; Topotecan; CPT-11; Doxorubicin; Daunomycin; Epirubicin; darubicin; mitoxantrone; losoxanti'one; Dactinomycin (Actinomycin D); amsacrine; pyi-azoloacridine; all-trans retinol; 14-hydroxy-retro-retinol; all-trans retinoic acid; N- (4- Hydroxyphenyl) retinamide; 13-cis retinoic acid; 3-Methyl TTNEB; 9-cis retinoic acid; fludarabine (2-F-ara-AMP); or 2-chlorodeoxyadenosine (2-Cda). Other anti-neoplastic compounds include, but are not limited to, 20-pi-1,25 dihydroxyvitaminD3; 5-ethynyluracil; abiraterone: aclarubicin; acylfulvene; adecypenol; adozelesin; aldesleuldn; all TK antagonists; alb-etamine; ambamustine; amidox; amifostine; aminolevulinic acid; amrubifiin; flezelastine; fluasterone; fludarabine; fluorodaunorunicin hydrochloride; forfenimex; formestane; fostriecin; fotemustine; gadohnium texaphyrin; gallium nitrate; galocitabine; ganii"elix; gelatinase inliibitors; gemcitabine; glutathione inhibitors; hepsulfani; heregulin; hexamethylenebisacetamide; homoharringtonine (HHT); hypericin; ibandronic acid; idarubicin; idoxifene; idramantone; ilmofosine; ilomastat; imidazoacridones; imiquimod; imniunostimulant peptides; insulin-like gro\^^h factor-1 receptor inhibitor; : interferon agonists; interferons; interleukins; iobenguane; iododoxombicin; ipomeanol, 4-; irinotecan; iroplact; irsogladine; isobengazole; isohomohalicondiin B; itasetron; jasplakinolide; kahalahde F; lamellarin-N tiacetate; ]ani*eotide; leinaraycin; lenograstim; lentinan sulfate; leptolstatin; letrozole; leukemia inhibiting factor; leukocyte alpha interferon; leuprolide + esn'ogen + progesterone; leuprorelin; levamisole; liarozole; linear polyamine analogue; lipophilic disaccharide peptide; lipophilic platinum compounds; lissoclinamide 7; lobaplatin; lombricine; lometrexol; lonidamine; losoxantrone; lovastatin; loxoribine; lurtotecan; lutetium texaphyrin; lysofylline; lytic peptides; maytansine; mamiostatin A; marimastat; masoprocol; maspin; matrilysin inhibitors; matrix metalloproteinase inhibitors; menogaril; merbarone; meterelin; metliioninase; metoclopramide; MIF inhibitqr; ifepristone; miltefosine; mirimostim; mismatched double stranded RNA; mithracin; mitoguazone; mitolactol; mitomycin analogues; mitonafide; mitotoxin fibroblast growth factor-saporin; mitoxantrone; mofarotene; molgi-amostim; monoclonal antibody, human chorionic gonadotrophin; monophosphoryl lipid A -^ myobacterium cell wall sk; mopidamol; multiple drug resistance gene inhibitor; multiple tumor suppressor 1-based therapy; mustard anticancer agent; mycaperoxide B; mycobacterial cell wall exti'act; myriaporone; N-acetyldinaline; N-substituted benzamides; nafarelin; nagrestip; naloxone -f pentazocine; napavin; naphterpin; nartograstim; nedaplatin; nemorubicin; neridronic acid; neutral endopeptidase; nilutamide; nisamycin; nitric oxide modulators; nitroxide antioxidant; nitrullyn; 06-benzylguaniiie; ,^ octreotide; okicenone; oligonucleotides; onapristone; ondansetroii; ondansetron; oracin; oral cytokine inducer; ormaplatin; osaterone; oxalipLaiini; oxaunomycin; paclitaxel analogues; paclitaxel derivatives; palauamine; palmitoylrhizoxin; pamidronic acid; panaxytriol; panomifene; parabactin: pazelliptine; pegaspargase; peldesine; pentosan polysulfate sodium; pentostatin; pentrozoJe; perflubron; perfosfamide; perillyl alcohol; phenazinomycin; phenylacetate; phosphatase inhibitors; picibanil; pilocarpdne hydrochloride; piraiiibicin; piriti'cxim; placetin A; placetin B; plasminogen activator inhibitor; platinum complex; platinum compounds; platinuia-triaznii^e complex; podophyllotoxin; porfimer sodium; porfiromycin; propyl bis-acridone; prostaglandin J2; proteasome inhibitors; protein A-based immune modulator; protein Idnase C inhibitor; protein kinase C inhibitors, niicroaI;gai: protein t>TOsine phosphatase inhibitors; purine nucleoside phosphor>"iase inhibitors; puipurins; pyrazoloacridine; p}^idoxylated hemoglobin polyoxyethylene conjugate; raf antagonists; raltitrexed; ramoseti*on; las faiiiesyl protein transferase inhibitors; ras inliibitors; ras-GAP inhibitor; retelliptine demethylated; rhenium Re 186 etidronate; rliizoxin; ribozymesu RII retinaniide; rogletimide; rohitukine; romurtide; roquinimex; rubiginone B 1: ruboxyl; safingol; saintopin; SarCNU; sarcophytol A; sargramostim; Sdi 1 mimetics; semustine; senescence derived inhibitor 1; sense oligonucleotides; signal transduction inhibitors; signal transduction modulators; single chain: antigen binding protein; sizofiran; sobuzoxane; sodium borocaptaie; sodiiizin phenylacetate; solverol; somatomedin binding protein; sonemiin; sparfosic acid; spicamycin D; spiromustine; splenopentin; spongistatin 1; squalamine: stem cell inliibitor; stem-cell division inhibitors; stipiamide; sti-omelysin inhibitors; sulfniosine; superactive vasoactive intestinal peptide antagonisn suradista; suramin; swainsonine; synthetic glycosaminoglycans; tallimustiiie; tamoxifen methiodide; tauromustine; tazarotene; tecogalan sodium; tegafurz tellurapyrylium; telomerase inhibitors; temoporfm; temozolomide; teniposioe: teti-achlorodecaoxide; teti'azomine; thaliblastine; thalidomide; thiocoraline: turombopoietm; thrombopoietm mimetic; tnymaltasm; tnymbpoietm receptor agonist; thymotiinan; thyroid stimulating hormone; tin ethyl etiopurpurin; tirapazamine; titanocene dichloride; topotecan; topsentin; toremifene; totipotent stem cell factor; translation inhibitors; tretinoin; triacetyluridine; triciribine; trimetrexate; triptorelin; tropisetron; turosteride; tyrosine Idnase inhibitors; t^xphostins; UBC inhibitors; ubenimex; urogenital sinus-derived growth inhibitory factor; urokinase receptor antagonists; vapreotide; variolin B; vector system, eiythi'ocyte gene therapy; velaresol; veramine; verdins; vertepoilfin; vinorelbine; vinxaltine; vitaxin; vorozole; zanoterone; zeniplatiii; zilascorb; and zinostatin stimalamer. X may also be an antiproliferative agent, for example piritrexiin isothionate. Alternatively, X may be an antiprostatic hypeitrophy agent such as, for example, sitogluside, a benign prostatic h^T^erplasia therapy agent such as, for example, tamsulosin hydrochloride, or a prostate gi'owth inhibitor such as, for example, pentomone. X can also be a radioactive agent, including, but not limited to: Fibrinogen ^^^I; Fludeoxyglucose ^^F; Fluorodopa ^^F; Insulin ^^^I; Insulin ^^^I; lobenguane 'I; lodipamide Sodium I; lodoantipyrine I; lodocholesterol ■•01 10*^ "i^^ I; lodohippurate Sodium ^I; lodohippurate Sodium " I; lodohippurate 1^1 10^ 1*^1 i*?"^ Sodium I; lodopyracet I; lodopyracet ' I; lofetamine Hydrochloride " I; lomethin ^"^I; lomethin ^^^I; lothalamate Sodium ^^^I; lothalamate Sodium ^^^I; tyrosine ^^^I; Lioth}a*onine ^"'"^I; Liothyi'onine ^^^I; Merisoprol Acetate *^'Hg; Merisoprol Acetate ^ Hg; Merisoprol Hg; Selenomethionine Se; Teclinetium ^^"^Tc Antimony Trisulfide Colloid; Technetium ^^"^Tc Bicisate; Technetium ^^^Tc Disofenin; Technetium ^^"^Tc Etidronate; Technetium ^^^Tc Exametazime; Technetium ^^""Tc Furifosmin; Technetium ^^"^Tc Gluceptate; Teclinetium ^^"'Tc Lidofenin; Technetium ^^"'Tc Mebrofenin; Teclinetium ^^"^Tc Medronate; Technetium ^^""Tc Medronate Disodium; Technetium ^^""Tc Mertiatide; Technetium ^^°'Tc Oxidronate; Technetium ^^""Tc Pentetate; Technetium ^^"^Tc Pentetate Calcium Trisodiuni; Technetium ^^^Tc Sestamibi; Teclmetium ^^""Tc Siboroxime; Technetmm ^^^Tc; Succimer; Tecl-metium ^^^Tc Sulftir Colloid; Technetium ^^^Tc Teboroxime; Technetium ^^"^Tc Tetrofosmin; Tecliiietium ^^"'Tc Tiatide; Thyroxine ^'^I; Thyroxine ^^^I; Tolpovidone ^'^^I; Triolein ^^^I; or Triolein ^^^L Therapeutic or cytotoxic agents may include, for example^ anti-cancer . Supplementary Potentiating Agents, including^ but not limited to: Tricyclic anti-depressant drugs (e.g.. imipramine, desipramine, amitryptyline, clomipramine, trimipramine, doxepin, nortriptyline, protiiptyline, amoxapine, and maprotiline); non-tricyclic anti-depressant drugs (e.g., serti'aline, trazodone, and citalopram); Ca-r-r antagonists (e.g., verapamil, nifedipine, nitrendipine, and caroverine); Calmodulin inliibitors (e,g., prenylamine, trifluoroperazine, and clomipramine): Amphotericin B; Triparanol analogues (e.g., tamoxifen); antian-h\i:hmic drugs (e.g., quinidine); antihypertensive dmgs (e.g., reserpine); Thiol depleters (e.g., buthionine and sulfoximine) and Multiple Drug Resistance reducing agents such as Cremaphor EL. The compounds of the invention also can be administered with cvtoldnes such as granuJocvte colony stimulating factor. Preferred anticancer agents used in anti-cancer cocktails (e.g., in combination with the agents of the invention) include (some with their MTDs show^^n in parentheses): gemcitabine (1000 mg/m"); methotrexate (15 gm/m" i.v. + leuco. leuco); 5-FU (500 mg/m'/day x 5days); FUDR (100 mg/kg x 5 in mice, 0.6 mg/lcg/day in human i.a.); FdUMP; Hydroxyurea (35 mg/lcg/d in man); Docetaxel (60-100 mg/ni'); discodermolide; epothilones; vincristine (1.4 mg/m"); vinblastine (escalating: 3.3-11.1 mg/nr, or rarely to IS.5 mg/m ); vinorelbine (30 mg/m^/wk); meta-pac; irinotecan (50-150 mg/m"",! x/wk depending on patient response); SN-38 (-100 times more potent than Irinotecan); 10-OH campto; topotecan (1.5 mg/mVday in humans, 1 x iv LD10mice==75 mg/m ); etoposide (100 mg/m in man); adriamycin; flavopiridol; Cis-Pt (lOOmg/m in man); carbo-Pt (360 mg/nr in man); bleomycin (20 mg/m2); mitomycin C (20 mg/m^); mithi-amycin (30 sug/lcg); t. capeciiaome {z.:> g/m" oraiiyj; cytaraome (^luu mg/m7dayj; 2-U-2'deoxyadeTiosiTie; FludaTabine-P04 (25 mg/m /day, x 5days); mitoxantrone (12-14 mg/m^); mitozolomide (> 400 mg/ra^); Pentostatin; or Tomudex. X may preferably be an antimetabolic agent, such as methotrexate, Ajitimetabelites include, but are not limited to, the following compounds and ' their derivatives: azathioprine, cladribine, cytarabine, dacarbazine, fludarabine phosphate, fluorouracil, gencitabine chlorhydrate, mercaptopurine, methotrexate, mitobronitol, mitotane, proguanil chlorohydrate, pyrimethamine, raltitrexed, trimetrexate glucuronate, urethane, vinblastine sulfate, vincristine sulfate, etc. More preferably, X may be a folic acid-t>pe antimetabolite, a class of agents that includes, for example, methotrexate, proguanil chlorhydrate, pyrimethanime, trimethoprime, or trimetrexate glucuronate, or derivatives of these compounds. In another embodiment, X may be a member of the anthi"acycline family of neoplastic agents, including but not limited to aclaiiibicine chlorhydrate, daunorubicine chlorhydrate, doxorubicine chlorhydrate, epirubicine chlorhydrate, idarubicine chlorhydrate, piraiiibicine, or zombi cine chlorhydrate. Furthemiore, X may be a camptothecin, or its derivatives or related compounds such as 10, 11 methylenedioxycamptothecin. Xmay also be selected from the maytansinoid family of compounds, which includes a variety of structurally related compounds. For example, ansamitocin P3, maytansine, 2'-N-demethylmaytanbutine, ormaytanbicyclinol are mavtansinoids. •/ The peptide agents of the invention can be modified or labeled to facilitate diagnostic or therapeutic uses. Detectable labels such as a ' radioactive, fluorescent, heavy metal, or other agents may be bound to the peptide agents of the invention. Single, dual, or multiple labeling of a peptide agent may be advantageous. For example, dual labeHng with radioactive iodination of one or more residues combined with the additional coupling of, for example,^^^ via a chelating group to amine-containing side or reactive groups, would allow combination labeling. This may be useful for specialized diagnostic needs such as identification of widely dispersed small neoplastic cell masses. Peptide analogs of the invention may also be modified, for example, by halogenation of the tyi'osine residues of the compound. Halogens include fluorine, chlorine, bromine, iodine, or astatine. Such halogenated peptide agents may be detectably labeled, e.g. if the halogen is a radioisotope such as, for example, '^F, ^^Br, "Br. ^"^I, '"^I, '^'l, '"l.. '=^1, ^^'l or ^"At. Halogenated compounds of the invention contain a halogen covalently bound to at least one amino acid, and preferably to D-Tyr residues in each peptide agent molecule. Other suitable detectable modifications include binding of other compounds (e.g., a fluorochrome such as fluorescein) to a lysine residue of the analog, particularly an analog having a linker including lysines. Radioisotopes for radiolabeling the biological peptide agents of the invention include any radioisotope that can be covalently bound to a residue of the analog. The radioisotopes can be selected fi*om radioisotopes that emit either beta or gamma radiation, or alternatively, the peptide agents can be modified to contain chelating groups that, for example, can be covalently bonded to lysine residue(s) of the analog. The chelating gi'oups can then be modified to contain any of a variety of radioisotopes, such as gallium, indium, technetium, ytterbium, rhenium, or thalhum (e.g., ^'^I, ^'Ga, ^^^In, ^^mTc, '\\ ^^^Re). \^Tiere the peptide agent is modified by attacliment of a radioisotope, preferable radioisotopes are those having a radioactive half-life corresponding to, or longer than, the biological half-life of the agent used. More preferably, the radioisotope is a radioisotope of a halogen atom (e.g. a radioisotope of fluorine, chlorine, bromine, iodine, and astatine), even more preferably ^Br, ^'Br, 'Bx, '\ '\ '\ '-% '-\ '\ or -"At. Conjugates that include radioactive metals are useful in radiographic imaging or radiotherapy. Preferred radioisotopes also include ^^"^Tc, ^^Cr, 'Ga, ^^Ga, ^^^In, ''\% ^^V 'Y, 'Y, ^^^Sm, ^^^o^^^^Dy, ^^Cu, '\u, ''RU, '^Rt, '^'RC, ^'?h, '^^Bi, '^-Bi, '^'Bi, and -^^Bi. The choice of metal is deteiTnined based on the desired therapeutic or diagnostic application. The metal complexes of the invention are useful as diagnostic and/or therapeutic agents. A detectable label may be a metal ion from heavy elements* or rare earth ions, such as Gd"' , Fe"* , Mn ", or Cr ". Conjugates that include paramagnetic or superparamagnetic metals are useful as diagnostic agents in MR] imaging applications. Paramagnetic metals that may be used in the conjugates include, but are not limited to, cliromium (III), manganese (II), iron (II). iron (III), cobalt (II), nickel (II), copper (II), praseodymium (III), neodymium (III), samarium (III), gadolinium (III), terbium (III), dysprosium (III), holmium (III), erbium (III), and ytterbium (III). Preferably, the polymer ' 111 has a relaxtivity of at least 10, 12, 15, or 20 niM" sec" Z', wherein Z is the concenti'ation of paramagnetic metal. Chelating groups may be used to indirectly couple detectable labels or other molecules to the peptide agents of the invention. Chelating gi-oups may link peptide agents with radiolabels, such as a bifunctional stable chelator may be linked to one or more tenninal or internal amino acid reactive groups. They may be linked via an isothiocyanate P-Ala or appropriate non a-anjino acid linker which prevents Edman degradation. Examples of chelators known in the art include, for example, the ininocarboxylic and polyaminopolycarboxylic reactive groups, DTPA (N,N-Bis[2-[bis(carboxymethyl)amino]ethyl]glycine), and DOTA (1,4,7,10-tetraaazacyclododecane-1,4,7,10-teti'aacetic acid). The cytotoxic or therapeutic conjugates of the invention can employ any of the large number of loiown somatostatin analogs that recognize the somatostatin receptor, e.g., those described in the definitions above. Preferably, the somatostatin analog portion of the conjugate contains between 10 and 18 amino acids, and includes the core sequence: cyclo[Cys-Phe-D-Trp-Lys-Tlir-Cys]. Preferably, the C-tenninus of the analog is: Thr-NH2. iiombesm analogs as disclosed herein may also be conjugated to cytotoxic or therapeutic agents in the peptide agents of the invention. The somatostatin analog can be coupled directly to the cytotoxic or therapeutic agent using known chemical methods, or the tAvo moieties can be coupled via an indirect linkage. For example, the analog may be attached to a chelating group that is attached to the cytotoxic or therapeutic agent. Chelating groups include, but are not limited to, an iminodicarboxyhc group or a polyaminopolycarboxylic group. For general mediods. see, e.g., Liu et al., Bioconjugate Chem. 12(4):653, 2001; Cheng et ai., WO 89/12631; IGeffer et. al, WO 93/12112; Albert et al., U.S.P.N. 5,753,627: and WO 91/01144 (each of which are hereby incorporated by reference). Specitlc targeting of labeled, therapeutic or c}^otoxic agents allows selective destruction of tumors expressing receptors specific for biologically active peptides. For example, the tumors expressing somatostatin receptors includes neoplasms of the lung, breast, prostate, colon, brain, gastrointestinal tract, neuroendocrine axis, liver, kidney, etc. (see Schaer et al., Int. J. Cancer, 70:530-537, 1997; Chave et ah, Br. J. Cancer 82(1 ):124-130, 2000; Evans et al, Br. J. Cancer 75(6):79S-803, 1997). Cytotoxic somatostatin peptide analogs may also be specific for tumor vasculatures, or angiogenic blood vessels, such as those which over-express somatostatin receptors (see Denzler and Reubi, Cancer 85:188-198, 1999; Gulec et al., /. Surg. Res. 97(2):131-137, 2001; Woltering et al., 1 Surg Res. 50:245, 1991/. Peptide agents of the invention may be administed to a mammalian subject, such as a human, directly or in combination with any phannaceutically acceptable carrier or salt Icnown in the art. PhaiTnaceutically acceptable salts ma\' include non-toxic acid addition salts or metal complexes that are commonly used in the phamiaceutical industr}'. Examples of acid addition salts include organic acids such as acetic, lactic, pamoic.. maleic, citric, mahp, ascorbic, succinic, benzoic, palmitic, suberic, salicyhc, tartaric, methanesulfonic, toluenesulfonic, or trifluoroacetic acids or the like; polymeric ■ r acids such as taimic acid, carboxymethyl cellulose, or the like; and inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid phosphoric acid, or the like. Metal complexes include zinc, iron, and the hke. One exemplary phamiaceutically acceptable carrier is physiological saline. Other physiologically acceptable carriers and their fomiulations are known to one skilled in the art and described, for example, in Remington's Pharmaceutical Sciences, (18^^ edition), ed. A. Gennaro, 1990, Mack Pubhshing Company, ■ Easton, PA. Phannaceutical fonnulations of a therapeutically effective amount of a peptide agent of the invention, or phamiaceutically acceptable salt-thereof, can be administered orally, parenterally (e.g., intramuscular, intoperitoneal, intravenous, or subcutaneous injection, inhalation, inti'adermally, optical drops, or implant), nasally, vaginally, rectally, sublingually, or topically, in admixture with a phamiaceutically acceptable earner adapted for the route of administration. Methods well known in the art for maldng fomiulations are found, for example, in Remington's Phairnaceutical Sciences (18^ edition), ed. A. Gennaro, 1990, Mack Publishing Company, Easton, PA. Compositions intended for oral use may be prepared in solid or liquid forms according to any method known to the art for the manufacture of phamiaceutical compositions. The compositions may optionally contain sweetening, flavoring, coloring, perfuming, and/or preserving agents in order to provide a more palatable preparation. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and gi'anules. In such sohd forms, the active compound is admixed with at least one inert phamiaceutically acceptable canier or excipient. These may include, for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, sucrose, starch, calcium phosphate, sodium phosphate, or kaolin. Binding agents, buffering agents, and/or lubricating agents (e.g., magnesium stearate) may also be used. Tablets and pills can additionally be prepared with enteric coatings. Liquid dosage forms for oral adminisfration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and soft gelatin capsules. These forms contain inert diluents commonly used in the art, such as water or an oil medium. Besides such inert diluents, compositions can also include adjuvants, such as wetting agents, emulsifying agents, and suspending agents." Formulations for parenteral administi-ation include sterile aqueous or non- aqueous solutions, suspensions, or emulsions. Examples of suitable vehicles include propylene glycol, polyethylene glycol, vegetable oils, gelatin, hydrogenated naphalenes, and injectable organic esters, such as ethyl oleate. Such fonnulations may also contain adjuvants, such as preserving, wetting, emulsifying, and dispersing agents. Biocompatible, biodegi-adable lactide polymer, lactide/glycolide copolymer, orpolyoxyethylene-polyoxypropylene copohTOers may be used to control the release of the compounds. Other potentially useful parenteral delivery systems for the polypeptides of the invention include ethylene-vinyl acetate copolynier panicles, osmotic pumps, implantable infiision systems, and liposomes. Liquid formulations can be sterilized by, for example, filtration through a bacteria-retaining filter, by incorporating sterilizing agents into the compositions, or by irradiating or heating the composiiions. Alternatively, they can also be manufactured in the fonn of sterile, solid compositions which can be dissolved in sterile water or some other sterile injectable medium immediately before use. Compositions for rectal or vaginal administration are preferably suppositories which may contain, in addition to active substances, excipients such as coca butter or a suppository wax. Compositions for nasal or sublingual administration are also prepared with standard excipients Icnown in the art. Formulations for inhalation may contain excipients, for example, Jactose, or maybe aqueous solutions containing, for example, polyoxyethylene-9-lauryl ether, glycocholate and deoxycholate, or may be oily solutions for administration in the form of nasal drops or spray, or as a gel. The amount of active ingredient in the compositions of the invention can be varied. One skilled in the ait will appreciate that the exact individual dosages may be adjusted somewhat depending upon a variety of factors, including the polypeptide being administered, the time of administi'ation, the route of administotion, the nature of the fomiulation, the rate of excretion, the ■ nature of the subject's conditions, and the age, weight, health, and gender of the patient. In addition, the severity of the condition targeted by the biologically active peptide such as somatostatin or bombesin will also have an impact on the dosage level. Generally, dosage levels of between 0.1 jJ-g/kg to 100 mg/kg of body weight are administered daily as a single dose or divided into multiple doses. Preferably, the general dosage range is between 250 |J.g/kg to 5.0 mg/lvg of body weight per day. Wide variations in the needed dosage are to be expected in view of the differing efficiencies of the various routes of administi'ation. For instance, oral administration generally would be expected to require higher dosage levels than administi'ation by intravenous injection. Variations in these dosage levels can be adjusted using standard empirical routines for optimization, which are well loiown in the art. In general, the precise therapeutically effective dosage will be detennined by the attending physician in consideration of the above identified factors. The polypeptides of the invention can be administered in a sustained release composition, such as those described in, for example, U.S.P.N. 5,672,659 and U.S.P.N. 5,595,760. The use of immediate or sustained release compositions depends on the type of condition being treated. If the condition consists of an acute or over-acute disorder, a treatnient with an immediate release fomi will be preferred over a prolonged release composition. Alternatively, for preventative or long-term treatments, a sustained released composition will generally be prefen-ed. Polypeptides of the present invention can be prepared in any suitable manner. The polypeptides may be isolated from naturally occuiiing sources, recombinantly produced, or produced synthetically, or produced by a combination of these methods. The synthesis of short peptides is well laiown in the art. See e.g., Stewart et al. Solid Phase Peptide Synthesis (Pierce Chemical Co., 2d ed., 19S4). The peptides of the present invention can be synthesized according to standard peptide synthesis methods loiown in the art and exempHfied in Example 1 below. The present invention is illustrated by the following examples, which are in no way intended to be limiting of the invention. EXAMPLE 1 Preparation of di-cesinm salt of (-^)-amethopterin (methotrexate). Methoti-exate (0.75 niniole) was dissolved in 200 ml of water to which was added cesium bicarbonate (1.5 mmol). The yellow solution was stirred for 4 hours, evaporated under reduced pressure, and the oily residue dissolved in ethanol. This was evaporated from anliydrous ethanol 3 times to remove residual water. EXAMPLE 2 Preparation of 2-bromo-acetyl-D-tert-butyl-Ser-D-tert-butyl-Ser-D-tert-butyl-Ser-D-tert-butyl-Ser'D-tert-butyl-Ser-epsilon-tert-but\1oxycarbonyl-Lys-D-tert-butyl-Tyi*-D-tert-buty^l-T}a"-S-trityl-Cys-Phe-D-Trprepsilon-tert- butyloxycarbonyl-Lys-tert-butyl-Thi"-S-tiity]-Cys-tert-butyl-Tlii'-Rink-amide-resin. Rink amide MBHA polystyrene resin (0.25 nimole) [4-(2',4'-dimethoxyphenyl-Fmoc-(aminomethyl)phenoxyacetamido-norleucyl-methylbenzhydrylamine resin, 100-200 mesh, Novabiochem, San Diego, CA] was added to the reaction vessel of a CS136 automatic peptide synthesizer (CS Bio, Inc., San Carlos, CA) and swollen in DMF for approximately 1 hour. The resin was filtered and an excess of 20% piperidine in DMF was added and mixed for 2 minutes. The resin was filtered and again an excess amount of 20% piperidine added and mixed for 20 minutes to ensure complete removal of the resin Fmoc group. After deprotection, the resin was w^ashed 4 times with DMF and then the first protected amino acid, Fmoc-Thr(tBut) (0.75 mmol), diisopropylcarbodiimide (DIG) (0.75 nmiol), and N-hydroxybenzotiiazole monohydrate (HOBt) (0.75 rmnol) were all dissolved in DMF and added to the resin which was mixed (1 h) followed by washing 4 times with DIvlF. The Fmoc group was again removed by treamient with 20% piperidine/DMF solution and, following the same general coupling procedures, the following amino acids were successively reacted with the growing peptide chain; Fmoc-S-trityl-L-cysteine, Fmoc-0-t-butyl-L-thireonine, N^-Fmoc-N^-Boc-L-lysine, N°-Fmoc-N'"-Boc-D-tr3qDtophan, Fmoc-L-pheny]alanine, Fmoc-S-trityl-L-cysteine, Fmoc-0-t-butyl-D-t}a-osine, Fmoc-0-t-butyl-D-tyrosine, N^-Fmoc-N^ -Boc-L-lysine, Fmoc-0-t-butyl-D-serine, Fmoc-0-t-butyl-D-serine, Fmoc-0-t-butyl-D-serine, Fmoc-0-t-bur\^]-D-serine, Fmoc-0-t-butyl-D-serine. After removal of the final Fmoc group, 2-bromoacetic acid was coupled to the N-tenninal amino group using the same coupling reagents. EXAMPLE 3 Preparation of methoti-exate-acetyl-D-tert-butyl-Ser-D-tert-butyl-Ser-D-tert-buiyl-Ser-D-tert-butyl-Ser-D-tei1-butyl-Ser-epsilon-tert-but}']oxycarbonyl-Lys-D-teit-butyi-Tyr-D-tert-butyl-Tyr-S-trityl-Cys-Phe-D-Trp-epsilon-tert-butyloxycarbonyl-Lys-tert-butyl-Thr-S-t-ityl-Cys-tert-butyl-Tlu'-Rink-amide-resin. The di-cesium salt of methotrexate (0.75 mmol) prepared in Example 1 was dissolved in DMSO and added to peptidyl resin (0.25 mmol) prepared in Example 2 in a round bottom flask. The suspension was gently mixed w-'liile heating in a water bath (40°C, 18 h), filtered, and washed with copious amounts of DMF followed by methanol. After a fmal filtration the derivatized resin was air dried overnight. EX^iMPLE 4 Preparation of methon-exate-acetyl-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-Lys-D- . TyT-D-T\T-cyclo[Cys-Phe-D-Trp-Lys-T]u-Cys]-ThT-amide. The methotrexate-peptide resin prepared in Example 3 (0.25 mmol) was placed in a round bottomed flask to which was added 15 ml of a solution of trifluoroacetic acid (TEA) containing water (2.5%), 1,2-ethanediThiol (2.5%), and tiiisopropylsilane (1%). The suspension was agitated (2 h), r^iltered, and washed several times with TEA. The TEA was evaporated in vacuo and ether added to the resulting oil to give a yellow powder which was then dissolved in 60% acetic acid (250 ml). A concenti'ated solution of iodine in methanol was added dropwise with vigorous stirring until a pennanent brown coloration was fomied whereupon excess iodine was removed by addition of a small quantity of ascorbic acid. The solution was reduced to a volume of around 10 ml in vacuo and the crude methotrexate peptide purified by preparative reverse phase high pressure liquid clu'omatography (RP-hplc) on a column (21.4 x 250 nmi) of C-18 bonded silica (D\Tiamax 300, 8 jim). A linear gradient elution system at a flov.^ rat of 20 niL/min was employed: buffer A consisted of 0.1% TEA and buffer B, 0.1% TEA m 80% MeCN; 20% B to 50% B was increased at 1% per min. The separation were monitored at 2S0nm. The fractions containing the pure product as evidenced by anah^ical hplc were pooled, concenti-ated in vacuo, and subjected to lyophiiization. The peptide v/as obtained as a fluffs^ wliite powder of constant weight by lyophihzation fi'om aqueous acetic acid. Correct composition was demonstrated by amino acid analysis of an acid hydrolysaie and matrix assisted laser desorption mass spectrometrv. EXAMPLE 5 Preparation of 2-bromO"acetyl-D4ert-butyl-SeMert-butyl-Ser-D-tert-buty^^ tert-butyl-Ser-D4ert-butyl'Ser4ei1-butyl-Ser-D-tert-butyl-Ser-tert-butyl-Ser-D- tert-butyl-Tyr-D-tert-butyl-Ser-Gln-Trp-Ala-Val-P-Ala-tert-butyloxycarbonyl- His-Phe-Nle-RiiLk-amide-resin. Rink amide MBHA polystyrene resin (0.25 mniole) [4-2\ 4'-dimethoxyphenyl-Fmoc-(aniinomethyl)phenoxyacetamido-norleucyl-methylbenzhydrylamine resin, 100-200 mesh, (Novabiochem, San Diego, CA] was added to the reaction vessel of a CS136 automatic peptide synthesizer (CS Bio, Inc., San Carlos, CA), and swollen in DMF for approximately 1 hour. The resin was filtered and an excess of 20% piperdine in DMF was added and mixed for 2 minutes. The resin was filtered and again an excess amount of 20% piperidine added and mixed for 20 minutes to ensure complete removal of the resin Fnioc gi'oup. After deprotection, the resin was washed 4 times with DMF and then the first protected amino acid, Fmoc-Nle (0.75 nnnol), diisopropylcarbodiimide (DIC) (0.75 mmol), and N-hydroxybenzotiiazole monohydrate (HOBt) (0.75 mmol) were all dissolved in DMF and added to the resin which was mixed (1 h) followed by washing 4 times with DMF. The Fmoc group w^as again removed by treatment with 20% piperidine/DMF solution and the remaining amino acid derivatives and 2 bromoacetic acid were coupled as described in Example 2 using the same coupling reagents. EXAMPLE 6 Preparation of methotrexate-acetyl-D-tert-butyl-Ser-tert-butyl-Ser-D-tert-butyl-Ser-tert-butyl-Ser-D-tert-butyl-Ser-tert-butyl-Ser-D-tert-butyl-Ser-tei-t-but}d-Ser-D-tert-butyl-Tyi--D-tert-butyl-Ser-Gln-Trp-Ala-Val-p-Ala-tert-butyloxycarbonyl-His-Phe-Nle-Rihk-amide-resin. The di-cesium salt of methoti'exate (0.75 mmol) prepared in Example 1 was dissolved in DMSO and added to peptidyl resin (0.25 mmol) prepared in Example 5 in a round bottom flask. The suspension was gently mixed w^hile heating in a water bath (40'C, 18 h), filtered, and washed with copious amounts of DMF followed by methanol. After a final filti'ation the derivatized resin was air dried overnight. EXAMPLE 7 Methoti-exate-acetyl-D-Ser-Ser-D-Ser-Ser-D-Ser-Ser-D-Ser-Ser-Tyi*-D-Ser- Gln-Trp-Ala-Val-p-Ala-His-Phe-Nle-NH.. The methotrexate-peptide resin prepared in Example 6 (0.25 mmol) was placed in a round bottomed flask to wliich w^as added 15 ml of a solution of mfluoroacetic acid (TEA) containing water (2.5%), L2 ethanedithiol (2.5%), and tiiisopropylsilane (1%). The suspension was agitated (2 h), filtered, and washed several times with TEA. The TEA was evaporated in vacuo and ether was added to the resulting oil to give a yellow powder. The methoti'exate peptide was purified by preparative reverse phase high pressure hquid clu-omatogi-aphy (RP-hplc) on a column (21.4x250 mm) of C-18 bonded silica (Dynamax 300m 8 [im). A linear gradient elution system at a flow rate of 20 niL/min was employed: buffer A consisted of 0.1% TEA and buffer B, 0.1% TEA in 80% MeCN; 20% B to 50% B was increased at 1%/min. The separation was monitored at 280 nm. The fractions containing the pure product as evidenced by analytical HPLC were pooled, concenti'ated in vacuo, and subjected to lyopliilization. The peptide was obtained as a fluffy wdiite powder of constant weight by lyophylization from aqueous acetic acid. Correct composition was demonstrated by amino acid analysis of an acid hydrolysate and matrix assisted laser desoipfion mass spectrometry'. EXAMPLES Effects of cytotoxic agent-peptide conjugates on tumor cell proliferation. A CellTiter 96 cell proliferation kit was used according to the described protocols (Promega Corporation, Madison, WI)). Culture medium (50 |il) containing various concenti-ations of different peptides was added respectively in each well of the 96-well kit plates followed by 50 |il of a suspension containing 5,000 cultured IMR-32 tumor cells. The plate was incubated at ^T'C for different times up to and including 7 days in a humidified, 5% COo annosphere. Kit dye solution (15 )il) was added to each Avell and the plate incubated the plates at 37^C for 4 hours in a humidified, 5%C02 atmosphere. After 4 hours, 100 (.LI of the solubilization / stop solution were added to each well and incubation was continued at ST^'C for 1 hour or more until complete solubilization of the fonnazan crystals occurred. Absorbencies of individual well solutions were then measured at 570 nm wavelength using a 96 well plate reader. EXAMPLE 9 In vitro effects of somatostatin analogs on rat pituitary GH release. This is a primary system for evaluating SRIF analog potency and can be considered a somatostatin subtype 2 rat receptor related system wliich historically also correlates well with human subtype 2 binding. Anterior pituitaries from adult male rats weighing 200-250g and housed under controlled conditions (lights on from 0500-1900h), are dispersed using aseptic techniques by a ti-\^sin/DNase method. The dispersed cells are diluted with sterile-filtered Dulbecco's modified Eagle medium (MEM) (Gibco Laboratories, Grand Island, NY (GIBCO)), which is supplemented with 2.5% fetal calf sei-um (GIBCO), 3% horse semm (GIBCO), 10% fresh rat serum (stored on ice for no longer than Ih) from the pituitary donors, 1% MEM nonessential amino acids (GIBCO), gentamycin (10 ng/ml; Sigma), and nystatin (10,000 U/ml; GIBCO). The cells are counted with a hemacytometer (approximately 2,000,000 cells per pituitary) and randomly plated at a density of 200,000 cells per well (Co-star cluster 24; Rochester Scientific Co., Rochester, NY). The plated cells are maintained in the above Dulbecco's medium in a humidified atmosphere of 95% air and 5% CO2 at 37° C for 961i. In preparation for a homione challenge, the cells are washed 3x with medium 199 (GIBCO) to remove old medium and floating cells. Each dose of secretagogue (diluted in siliconized test tubes) was tested in quadruplicate wells in a total volume of 1 ml medium 199 containing 1% BSA (fraction V; Sigma Chemical Co., St Louis, MO). Cells are pulsed with SS or SS analogs doses in the presence of GH-stimulatory InM GRH(1-29)NH2. After 3h at 37°C in an air/carbon dioxide atmosphere (95/5%), the medium is removed and stored at 20*^0 until assayed for honnone content. GH in plasma and media is measured by a standard double antibody RIA using components supplied by the NIDDK and the National Homione and Pituitary Program. EXAMPLE 10 Preparation of O-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser 0-benzyl-D-Ser-0-benzyLD-Ser-L-Nle-0-2,6-dichloroben2yl-D-TyT-0-benzyl-D-Ser-S-4-methYlbenzyl-L'Cys-L-Phe-D-Trp-N^-(2-chiorobenzyloxycarbonyI)-L-Lys-0- benzyl-L-Thr-S-4-methylbenzyl-L-Cys-O-benzyl-L-Thr-MBHA resin. Methyibenzhydrylamine (MBHA) polystyrene resin (Bachem, Inc., Torrance. CA) (0.25 nmnole) was added to the reaction vessel of a CS136 automatic peptide synthesizer (CS Bio, Inc., San Carlos, CA) and swollen in methylene chloride (DCM) for approximately 1 hour. The resin was filtered and an excess of 10% diisopropylethylamine (DIPEA) was added and mixed for two minutes. The resin was filtered and again an excess amount of 10% DIPEA added and mixed for 5 minutes to ensure complete neutralization of the resin. After neutralization, the resin was washed 4 times with DCM and then the first protected amino acid, Boc-Thr(Bzl)-OH (0.75 mmol), diisopropylcarbodiimide (DIC) (0.75 mmol), and N-hydroxybenzotiiazole monohydrate (HOBt) (0.75 mmol) were all dissolved in DMF and added to the resin which was mixed (1 h) followed by washing 4 times with DCM. The tBoc group was removed by adding an excess of 40% Trifluoroacetic Acid (TFA) DCM and mixed for 2 minutes. The resin was filtered and again an excess amount of 40% TFA added and mixed for 20 minutes to ensure complete removal of the N-temiinal tBoc. The resin was filtered and an excess of 10% diisopropylethylamine (DIPEA) was added and mixed for two minutes. The resin was filtered and again an excess amount of 10% DPEA added and mixed for 5 minutes to ensure complete neutralization of the resin. After neutralization, the resin was washed 4 times with DCM and then following the same general coupling procedures, the following amino acids were successively reacted with the gi-owing peptide chain: Boc-S-4-methylbenzy]-L-cysteine, Boc-0-benzyl-L-thi'eonine, N^-Boc-N^-(2-chlorobenzyloxycarbonyl)-L-lysine, Boc-D-tiyptophan, Boc-L-phenylalanine, Boc-S-4-methylbenzyl-L-cysteine5Boc-0-benzyl-D-serine, Boc-0-2,6-dichlorobenzyl-D-tyrosine, Boc-norleucine., Boc-0-benzyl-D-serine, Boc-0-benzyl-D-serine, Boc-0-benzyl-D-serine, Boc-0-benzyl-D-serine, Boc-0-benzyl-D-seiine. The resin was finally washed 4 times with methanol and left ovemight to dry. EXAMPLE 11 Preparation of D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-L-Norleucine-D-Tyr-D-Ser -cyclo[L-Cys-'L-Phe-D-Tip-L-Lys-L-Thi'-L-Cys]-L-Tlir-NH2. The peptidyl resin from Example 10 along with 5 mL of anisole was placed in a Teflon apparatus appropriate for anhydrous hydrogen fluoride manipulation. The reaction vessel was cooled in an alcohol/dry ice bath for^5 minutes and then 35mL of gaseous anhydrous fluoride (HF) was condensed into the reaction vessel. The bath was changed from dry ice to regular ice and allowed to mix for one hour, then the HF was purged from the reaction vessel with a stream of nitrogen. The peptide was precipitated 3 times with excess ethyl ether and filtered. The fihered, crude peptide was dissolved in 60-90 percent acetic acid (250 ml). A concenti*ated solution of iodine in methanol v\^as added dropwise with vigorous sxiixing until a permanent brown coloration was fomied whereupon excess iodine was removed by addition of a small quantity of ascorbic acid. The solution was reduced to a volume of around 10 ml in vacuo and the ciude peptide purified by preparative reverse phase high pressure liquid chromatography (RP-hplc) on a cohmm {21.4 x 250 mm) of C-18 bonded sihca (DvT.amax 300. 8 um). A linear gradient elution s}'stem at a flow rate of 20 mL/min was employed: buffer A consisted of 0.1% TFA and buffer B, 0.1% TFA in 80% MeCN; 20% B to 50% B was increased at 1 % per minute. The separations were monitored at 2S0nm. The fractions containing the pure product as evidenced by ana]\l:icaJ HPLC were pooled, concentrated in vacuo and subjected to lyophilization. The peptide w^as obtained as a fluffy white powder of constant weight by lyophilization from aqueous acetic acid. Con'ect composition was demonstrated by amino acid analysis of an acid hydrolysate and matrix assisted laser desorption mass spectromenw. EXAMPLE 12 Preparation of D'Ser-D-Ser-D^Ser-D-Ser-D-Ser-L-Lys-3"''I-D-T}'T-D-Ser-cycIo[L-Cys-L-Phe-D-Trp-L-Lys-L.Thr-L-Cys]"L-Thi--NH2. A niodified Chloramine-T reaction was used to iodinate the peptide prepared in Example 11. Phosphate buffer (200 pL of 0-05M) was added to a septum-sealed vial containing 20 mCi of ""iodine and this served as the reaction vessel. Once neutralized, 9.411 x 10"" moles of peptide dissolved in 100 nL phosphate buffer were injected into the reaction vial. To start the iodination reaction, 4.29 x lO"'^ moles of chloramine-T were injected into the reaction vial in 50 \xL of buffer. The reaction vessel was vortexed rapidly for 15-20 seconds and then the reaction halted by injecting 4.3 x 10'^ moles of sodium metabisulfite in 50 |-iL. Purification: A CI 8 SepPak Lite caitridge (Waters Corp., Milford, Mass.) was used to purify the peptide from reactants. The SepPak was activated by washing with 10 mL of absolute ethanol at a flow rate of 1 mL / min. The SepPak was then washed with 10 mL of H2O. The radioactive reaction mixture was then apphed to the SepPak followed by 3 x 3-mL washes of the reaction vessel with 5% ethanol. The peptide was separated from the rest of the reactants by washing the SepPak with 10 mL of 20% ethanol. The peptide was finally eluted off the column in 250 uL aUquots using a solution of 80% ethanol in 0.01 N HCL and collected into 2 mL sterile screw cap vials. EXAMPLE 13 Preparation of O-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser-G-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser-0-ben2yl-D-Ser-N^-(2-chlorobenzyloxycarbonyl)-L-Lys-0-2,6-dichlorobenzyl-L-Tyr-0-2,6-dichloroben2yl-L-Tyr-S-4-methylbenzyl-L-Cys-L-Phe-D-Trp-N^-(2-chlorobenzyloxycarbonyl)-L-Lys-0-benzyl-L-Thi--S-4-methylbenzyl-L-Cys-0-benzyl-L-Thr-MBHA resin. Methylbenzhydrylamine (MBHA) pol^^styrene resin (Bachem, Inc., Torrance. CA) (0.25 mniole) was added to the reaction vessel of a CS136 automatic peptide synthesizer (CS Bio, Inc., San Carlos, CA) and swollen in methylene chloride (DCM) for approximately 1 hour. The resin was filtered and an excess of 10%) diisopropylethylamine (DEPEA) was added and mixed for two minutes. The resin was filtered and again an excess amount of 10%9, DPEA added and mixed for 5 minutes to ensure complete neutralization of the resin. After neutralization, the resin was washed 4 times with DCM and then the first protected amino acid, Boc-Tlir(Bzl)-OH (0.75 mmol), diisopropylcarbodiiniide (DIC) (0.75 nimol), andN-hydroxybenzotriazole monohydrate (HOBt) (0.75 mmol) were all dissolved in DMF and added to the resin which was mixed (] h) followed by washing 4 times with DCM. The tBoc group w^as removed by adding au excess of 40% trifluoroacetic acid (TFA) DCM and mixed for 2 minutes. The resin was filtered and again an excess amount of 40% TFA added and mixed for 20 minutes to ensure complete removal of the N-terminal tBoc. The resin was filtered and an excess of 10% diisopropyiethylamine (DIPEA) was added and mixed for two minutes. The resin was filtered and again an excess amount of 10% DIPEA added and mixed for 5 minutes to ensure complete neutralization of the resin. After neuti'ahzation, the resin was washed 4 times with DCM and then following the same general coupling procedures, the following amino acids were successively reacted with the growing peptide chain Boc-S-4-methy]ben2yl-L-cysteine. Boc-0-benzyl-L-thi-eonine^ N°-Boc-N^-(2-chlorobenzyloxycarbonYl)-L-lysine, Boc-D-ti*yptophan, Boc-L-phenylalanine. Boc-S-4-methylbenzyl-L-cysteine, Boc-0-2,6-dichIorobenzyl-D-t}Tosine, Boc-0-2,6-dichlorobenzyl-D-t)Tosine, N^-Boc-N^ -(2-chlorobenzyloxycarbonyl)-L-lysine, Boc-0-benzyl-D-serine, Boc-0-benzyl-D-serine, Boc-0-benzyl-D-serine, Boc-O-benzyl-D-serine, Boc-O-benzyl-D-serine, Boc-O-benzyl-D-serine, Boc-0-benzyl-D-serine, Boc-O-benzyl-D-serine, Boc-O-benzyl-D-serine. Boc-0-benzyl-D-serine. The final Boc group was removed, the peptide neutralized, and w^ashed using the same general procedure as above. EXAMPLE 14 Preparation of DOTA-O-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser-O-benzyl-D-Ser-0-benzyl-D-Ser-0-benzyl-D-Ser-N^-(2-chl.orobeB2yloxycarbonyl)-L -Lys-0-2,6-dichlorobenzyl-L-Tyr-0-2,6'dich]orobeiizyl-L-Tyi--S-4-methylbenzyl-L-Cys--L-Phe-D-Trp-N^-(2-chlorobenzyloxycarbonyl)-L-Lys- O-benzyl-L-Tlir-S-4-methylbenzyl-L-Cys-O-benzyI-L-Thr-MBHA resin. In order to couple DOT A, which is very insoluble in organic solvents including DMF and DMSO alone, to the fi*ee amino group of the growing chain, a novel procedure utilizing the unexpected solubilizing effects of HOBt was used. First, 5 mmol of HOBT was dissolved in a beaker containing 50-75 ITLL of DMSO5 then 1.25 mmol of DOTA were added and the suspension vigorously mixed until the DOTA went into solution, DIG (1.25 niniol) was added to the beaker and this mixture was added to the peptidyl resin , mixed overnight, and then washed 4 times with DMF and 4 times with methanol. EXAMPLE 15 Preparation of DOTA-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-L-Lys-D-Tyr-D-Tyi--cydo[L-Cys-L-Phe-D-Trp-L'Lys-L-Tlu--L- Cys]-L-Thi--NH2. The protected peptide resin described in Example 14 was subjected to cleavage fi'om the resin and removal of side-chain protecting groups using liquid HP as described in Example 12. The free peptide was then cyclized and purified also as described in Example 12. EXAMPLE 16 Preparation of D-O-benzyl-Ser-O-benzyl-Ser-D-O-benzyl-Ser-O-benzyl-Ser-D-0-benzyl-Ser-0-benzyl-Ser-D-0"benzyl-Ser-0-benzyl-Ser-D"0" dichlorobenzy]-Tyi-D-0-benzyl-Ser-Gln-Trp-Ala-Val-p-Ala-tosyl-His-Phe- -Nle-MBHA resiii. Methylbenzhydrylamine (MBHA) polystyrene resin (Bachem, Inc., Torrance. CA) (0.25 mmole) was added to the reaction vessel of a CS136 automatic peptide synthesizer (CS Bio, Inc., San Carlos, CA) and the peptide was assembled by successive additions of amino acid derivatives as described in Example 13. EXAMPLE 17 D-Ser-Ser-D-Ser-Ser-D-Ser-Ser-D-Ser-Ser-D-T}n:-D-Ser-Ghi-Tip-A]a-Val-[3-Ala-His-Phe-Nle-NH2. The protected peptide resin described in Example 16 was subjected to cleavage from the resin and removal of side-chain protecting groups using liquid HF as described in Example 12. The free peptide was then purified also as described in Example 12. EXAMPLE 18 In vitro effects of bombesin agonist analogs on guinea pig pancreatic acinar cell amylase release. Dispersed acini from one guinea pig pancreas were suspended in 150 ml of standard incubation solution and samples (250 ml) were incubated for 30 min at 37°C, and amylase release was detennined by the Phadebas reagent method. Amylase release was calculated as the percentage of amylase activity in the acini at the beginning of the incubation that was released into the extracellular mediiim during xlTe incubation. Various concentrations of bombesin standard and analogs were incubated at various concenti'ations in order to determine half-maximal stimulation values (EC^o)- EXAMPLE 19 Biodistribution of ^^'l labeled JF-08-73 (Succinate-D-Asp-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Asp-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-L-Lys-D-TvT-D-Tyr-cyclo[L-Cys-L-Phe-D-Trp-L-Lys-L-Tlu--L-Cys]-L-Thi--NH2 and JF-08o3 (D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-L-Lys-D-Tyr-D-Ser-cyclo[L-Cys-L-Phe-D-Trp-L-Lys-L-Tlir-L-Cys]-L-Thi--NH2. The peptides were radiolabeled as described in Example 12. The second screw cap vial containing the highest amounts of radioactive peptide was diluted with phosphate buffered saline to achieve a fmal concentration of less than 3% ethanol. The solution was divided into tluee equal parts not exceeding 2 mL and injected intraperitoneally into each rat. Urine and feces were collected on an adsorbent pad overnight. At 24 hours, the rats were killed, dissected and each of the below organs were weighed and counted in a dose calibrator. The results are shown in Fig. 2. EXA.MPLE 20 Preparation of thiocolchicine. Colchicine (1.25 mraole) was dissolved in 10.0 mL of water to which was added sodium methanethiolate (7.13 mmol). The yellow solution was stirred for 24 hours, then extracted 3x with ETOH:Ch]orofomi (1:1), then evaporated to yield the desired compound as yellow cr}^stals. EXAMPLE 21 Preparation of deacetylthiocolcliicine. To the product from Example 1, 5.0 mL of methanol and 5.0 niL of 2N. HC] were added and the solution refluxed 18 hours under dry nitrogen. The methanol was distilled off, the residual solution was reneutralized with NaOH, extracted 3 times with chloroform, evaporated, and finally lyophihzed fi*om acetonitiile/water as a yellow powder. EXAMPLE 22 Preparation of deacetylthiocolchicine-3-thiodiproprionyl-N^-(2-chloroben2yloxycarbonyl)-L-Lys-0-benzyl-D-Ser-0-benzyl-D-Ser-0-benzyl-D-Ser-O-beiizyl-D-Ser-O'benzyl-D-Ser^O-benzyl-D-Ser-O-benzyl-D-Ser-0-benzyl-D-Ser- 0-benzyl-D-Ser-0-benzyLD-Ser-L-Nle-0-2,6-dichlorobenzyl-D-TvT-0-benzyl-D-Ser-S-4-methylbenzyI-L-Cys-L-Phe-D-Trp-N'-(2" chloroben2yloxycarbonyl)-L-Lys-0-ben2yl-L-Thr-S-4-methylben2yl-L-Cys-0-benzyl-L-Thr-MBHA resin. Methylenzhydrylamine (MBHA) polystyi'ene resin (Bachem, Inc., Tori'ance, CA) (0.25 mmole) was added to the reaction vessel of a CS136 automatic peptide synthesizer (CS Bio, Inc., San Carlos, CA) and swollen in methylene chloride (DCM) for approximately 1 hour. The resin was filtered and an excess of 10% diisopropylethylamine (DIPEA) was added and mixed for two minutes. The resin was filtered and asain an excQss amount of 10% DIPEA added and mixed for five minutes to ensure complete neutralization of the resin. After neuti'alization, the resin was washed 4 times with DCM and then the first protected amino acid, Boc-Thr(Bzl)-OH (0.75 mmol), diisopropylcarbodiimide (DIG) (0.75 mmol), and N-hydroxybenzotriazole monohydrate (HOBt) (0.75 imnol) were all dissolved in DMF and added to the resin which was mixed (1 h) followed by washing 4 times with DCM. The tBoc group was removed by adding an excess of 40% Trifluoroacetic Acid (TFA) DCM and mixed for 2 minutes. The resin was filtered and again an excess amount of 40% TFA added and mixed for 20 minutes to ensure complete removal of the N-temiinal tBoc. The resin was filtered and an excess of 10% diisopropylethylamine (DIPEA) was added and mixed for two minutes. The resin was filtered and again an excess amount of 10% DIPEA added and mixed for 5 minutes to ensure complete neutralization of the resin. After neutralization, the resin was washed 4 times with DCM and then following the same general coupling procedures, the following amino acids were successively reacted with the growing peptide chain: Boc-S-4-methylbenzyl-L-cysteine, Boc-0-benzyl-L-threonine, N°-Boc-N^-(2-chloroben2yloxycarbonyl)-L-lysine. Boc-D-tryptophan, Boc-L-phenylalanine, BoC'S-4-methylbenzyl-L-cysteine, Boc-0-benzyl-D-serine, Boc-0-2,6-dichlorobenzyl-D-tyrosine, Boc-norleucine, Boc-0-benzyl-D-serine, Boc-0-benzyl-D-serine, Boc-0-benzyl-D-serine, Boc-O-benzyl-D-serine, Boc-0-benzyl-D-serine, Boc-0-benzyl-D-serine, Boc-0-benzyl-D-serine, _Boc-0-benzyl-D-serine, Boc-0-benzyl-D-serine, Boc-0-benzyl-D-serine, N^-Boc-N^-(2-chlorobenzyloxycarbonyl)-L-lysine, 3-thiodiproprionic acid, and finally without the tBoc deprotection step, deacetylthiocolchicine was coupled in DCM/Dic. The resin was finally washed 4 times with methanol and left overnight to dry. EXAMPLE 23 Preparation of Deacety]thiocoIchicme-3~thiodiproprionyl-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-D-Ser-L-Norleuciiie-D-Tyi'-D-Ser-cyclo[L-Cys-L-Phe-D-Tip-L-Lys-L-Tlir-L-Cys]-L-Tlir-NH2. The peptidyl resin fron:i Example 10 along with 5 noL of anisole was placed in a Teflon apparatus appropriate for anhydrous hydrogen fluoride manupulation. The reaction vessel was cooled in an alcohol/dry ice bath for 5 minutes and then 35 niL of gaseous anhydrous fluoride (HF) w^as condensed -into the reaction vessel. The bath was changed from drv ice to regular ice and allowed to mix for one hour, then the HF was purged from the reaction vessel with a sti*eam of nitfogen. The peptide was precipitated 3 times with excess ethyl ether and filtered. The filtered, crude peptide was dissolved in 60-90 percent acetic acid (250 nil). A concentrated solution of iodine in methanol was added dropwise with vigorous stimng until a pennanent brown coloration was fomied whereupon excess iodine was removed by addition of a small quantity of ascorbic acid. The solution was reduced to a volume of around 10 ml in vacuo and the crude peptide purified by preparative reverse phase high pressure liquid cloromatography (RP-hplc) on a column (21.4x250 mm) of C-18 bonded sihca (Dynamax 300, 8 p.m). A linear gradient elution system at a f].ow rate of 20 ml/min was employed: buffer A consisted of 0,1% TFA and a buffer B, 0.1% TFA in S0%o MeCN; 20%o B to 50%) B was increased at 1% per mmute. The separations were monitored at 2S0nm. The fractions containing the pure product as evidenced by analytical HPLC were pooled, concenti'ated in vacuo and subjected to lyophilizaiion. The peptide was obtained as a fluffy yellow powder of constant weight by lyophilization from aqueous acetic acid. Correct composition Avas demonstrated by amino acid analysis of an acid hydrolysate and matrix assisted laser desorption mass specti'ometry. EXAMPLE 24 Preparation of the acyl chloride of camptothecin. Camptothecin (0.574 nimole) was suspended in 30 mL anhydrous DCM in a 100 niL RB flask. To this slurry, DMAP (2,455 mmole) dissolved in 20 " mL anhydrous DCM was added over 20 minutes at 0°C under a dry nitrogen atmosphere. Phosgene (0.965 mmole) was added to the sluiTy and mixed for 30 minutes at O'^C and 2 hours at RT. Excess phosgene and methylene chloride were evaporated and the acyl chloride of camptothecin dissolved in metylene chloride. EXAMPLE 25 Preparation of Camptothecin-carbonyLSar-D-tert-butyl-Ser-Norleucine-D-tert-butyl-Tyr-D-tert-buty]-Ser-S-trityl-Cys-Phe-D-Trp-epsilon-tert-butyloxycarbonyl-Lys-tert-butyl-Tlu-S-trityl-Cys-tert-butyl-Thr-Rink-amide-resin. Rink amide MBHA polystyrene resin (0.063 mmole) [4'{2\ 4'-dimethoxyphenyl-Fmoc-(aminomethyl)phenoxyacetamido-nor]eucyl-methylbenzhydrylamine resin, 100-200 mesh, Novabiochem, San Diego, C] was added to the reaction vessel of a CS136 automatic peptide synthesizer (CS Bio, Inc., San Carlos, CA) and swollen in DMF for approximately 1 hour. The resin was filtered and an excess of 20% piperidine in DMF was added and mixed for 2 minutes. The resin was filtered and again an excess amount of 20% piperidine added and mixed for 20 minutes to ensure complete removal of •. the resin Fmoc group. After deprotection, the resin was washed 4 times with DMF and then the first protected amino acid, Fmoc-Tlir(tBut) (0.188 mmol), diisopropylcarbodiimide (DIC) (0.188 mmol), andN-hydroxybenxotriazole monohydrate (HOBt) (0.188 mmol) were all dissolved in DMF and added to the resin which was mixed (1 h) followed by washing 4 times with DMF. The Fmoc gi'oup was again removed by ti*eatment with 20% piperidine/DMF solution and, following the same general coupling procedures, the following amino acids were successively reacted with the growing peptide chain; Fmoc-S-trityl-L-cysteine^Fmoc-O-t-hutyl-L-threonine-N^^-Fmoc-N^" Boc-L-lysine, N^-Fmoc-N^^-Boc-D-ti'yptophan, Fmoc-L-phenylalanine, Fmoc-S-trity]-L-cysteine, Fmoc-O-t-butyl-D-serine, Fmoc-O-t-butyl-D-tyi'osine, N*^-Fmoc-norleucinej Fmoc-O-t-butyl-D-serine, Fmoc-sarcosine. After removal of the final Fmoc group, Camptothecin acyl chloride from EXAMPLE 24 was added to the resin and mixed overnight, washed with copious amounts of DMF followed by DCM then methanol. After a final filtration the derivatized resin air dried overnight. EXAiMPLE 26 Preparation of camptothecin-carbonyl-Sar-D-Ser-Nle-D-T)T-D-Ser-cyclo[Cys-Phe-D-Trp-Lys-Thr-CysJ-Thr-amide, The camptothecin-peptide resin prepared in EvXample 25 (0,063 mmol) was placed in a round botiomed flask to which was added 15 ml of a solution of n-ifluoroacetic acid (TFA) containing water (2.5%), 1,2-ethanedithiol (2.5%), and triisopropylsilane (1%). The suspension was agitated (2 h), filtered, and washed several times with TFA. The TFA was evaporated in vacuo and ether added to the resulting oil to give a yellow powder which was then dissolved in 60% acetic acid (250 ml). A concentrated solution of iodine in methanol was added dropwise with vigorous stining until a permanent brown coloration was formed whereupon excess iodine was removed by addition of a small quantity' of ascorbic acid. The solution was reduced to a volume of around 10 ml in vacuo and the crude camptothecur peptide purified by preparative reverse phase high pressure liquid chromatography (RP-hplc) on a colunrn (21.4 x 250 mm) of C-18 bonded silica (Dynamax 300, 8 [im). A linear gradient elution system at a flow rate of 20 mL/min was employed: buffer A consisted of 0.1 % TFA and buffer B, 0.1% TFA in 80% MeCN; 20% B to 50% B was increased at 1% per min. The separation were monitored at 280nm. The fractions containing the pure product as evidenced by analytical hplc were pooled, concentrated in vacuo, and subjected to lyphilization. The peptide was obtained as a fluffy white powder of constant weight by lyphilization from aqueous acetic acid. Con-ect composition was demonsti-ated by amino acid analysis of an acid hydrolysate and matrix assisted laser despoiption mass spectrometry. Other Embodiments; Although the present invention has been described with reference to preferred embodiments, one skilled in the art can easily ascertain its essential characteristics and, without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Those skilled in the an will recognize or be able to ascertain using no more than routine experimentation^ many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed in the scope of the present invention. All publications, patents, and apphcations mentioned in the specification are herein incorporated by reference. We claim: Claims 1. A peptide agent having the fommla: X-Y-Z-Q, wherein: X is selected from the group consisting of cytotoxic agents, therapeutic agents, detectable labels, and chelating groups, or is omitted; Y is a peptide that increases the hydrophilic biodistribution of said agent a , hydrophilic polymer that inchides a linker for X, or is omitted; Q is a peptide having biological activity; and Z is a linldng peptide that, when bonded to Q at the N-terminus or at a compatible side-chain amino group of Q, preserves at least 50% of the biological activity of Q, Z having the fonmila: A-B-C-E-F, wherein: A is D-Lys, D-Tyr, D-Ser, or L-Ser, or is deleted; B is D-Lys or D-T}a", or is deleted; C is Lys, Ser, hSer, Thr, Nle, Abu, Nva, (2, 3, or 4) 3-p3a'idyl-Ala (Pal), Om, Dab, Dap, 4-NH2-Phe, D-4-OH-Pro, or L-4-OH-Pro, or is deleted; E is D-Lys, D-Tyi', D-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyi-, 3-5 diiodo-D-Tyi", 3-astatine-D-Tyr, 3-5 astatine-D-Tyr, 3-bromo-D-Tyr, 3-5 dibromo-D-Tyi-, D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Gln; and F is D^Lys, D-Tyi-, D-Ser, L-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyr, 3-5 diiodo-D-Tyr, 3-astatine-D-Tyr, 3-5 astatine-D-Tyr, 3-bromo-D-Tyr, 3-5 dibromo-D-TyT, D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-GIu, D-Gln, orL-Gln; provided that when A, B, C, and E are Tyr, Tyr, Lys, and Tyr, respectively, F is not Lys; and when A, B, C, and E are Lys, Tyr, Lys, and Tyr, respectively, E is not T}T or Lys; and when A and B are deleted, and C and E are Lys and Tyi', respectively, F is not Tyr or Lys. 2. A peptide agent having the fomiula: X-Y-Z-Q, wherein: X is a cytotoxic agent or a therapeutic agent; Y is a peptide that increases the hydrophilic biodistribution of said agent, a hydrophilic polymer that includes a linlcer for X, or is omitted; Q is a peptide having biological activity; and Z is a linldng peptide that, when bonded to Q at the N-tenninus or at a compatible side-chain amino gi'oup of Q, presei-ves at least 50% of the biological activity of Q, Z having the fomiula: A-B-C-E-F, wherein: A is D-Lys, D-Tyi-, D-Ser, or L-Ser, or is deleted; B is D-Lys or D-Tyr, or is deleted; C is Lys, Ser, hSer, Tlir, Nle, Abu, Nva, (2, 3, or 4) 3-pyridyl-Ala (Pal), Om, Dab, Dap, 4-NH2-Phe, D-4-OH-Pro, or L-4-OH-Pro, or is deleted; E is D-Lys, D-Tyr, D-Ser, D-4.0H-Pro, L-4-OH-Pro, 3-iodo-D-Tyr, 3-5 diiodo-D-Tyr, 3-astatine-D-Tyi-, 3-5 astatine-D-Tyr, 3-bromo-D-Tyr, 3-5 dibromo-D-Tyr, D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Gln; and F is D-Lys, D-Tyr, D-Ser, L-Ser, D-4-OH-Pro;L-4-OH-PTO, 3-iodo-D-Tyr, 3-5 diiodo-D-Tyr, 3-astatine-D-Tyr, 3-5 astatme-D-Tyi-, 3-bromo-D-Tyr, 3-5 dibromo-D-Tyi-, D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Gln; provided that when A, B, C, and E are Tyi-, T>a:, Lys, and Tyi', respectively, F is not Lys; and when A, B, C, and E are Lys, Tyi*, Lys, and Tyr, respectively, E is not T\T or Lys; and when A and B are deleted, and C and E are Lys and Tyr, respectively, F is not Tyr or Lys. 3. The peptide agent of claim 2, wherein Y is a peptide that increases the hydrophilic biodistribution of said agent. 4. The peptide agent of claim 3, wherein Y is of the formula: U(V-V)n, wherein: U is D-Pro, L-Pro, D-4-OH-Pro, L-4-OH-Pro, Sar, or (NHo-(CH2)m-C00H) where m=2-10, inclusive, or is deleted; each V is independently selected fi'om the group consisting of: D-Ser, L-Ser, D-Thr, L-Thr, D-Gln, L-Gln, D-Asn, L-Asn, D-4-OH-Pro, and L-4-OH-Pro; and n is an integer from 1 to 50, inclusive. 5. The peptide agent of claim 4, wherein each V is independently D-Ser or L-Ser. 6. The peptide agent of claim 2, wherein Y is a hydropliilic polymer. 7. The peptide agent of claim 6, wherein Y is polyethylene glycol, polyvinyl acetate, pol}^inyl alcohol, HPMA (N-(2-hydroxypropyl) methacrylamide) or HPTv^IA copolymers, a, (3-poly(N-hydroxyethyl)-DL-aspartamide (PHEA), or a, p-poly(N-hydroxypropyl)-DL-aspartamide. 8. The peptide agent of claim 2, wherein X is a cytotoxic agent. 9. The peptide agent of claim 8, wherein X is an antimetabolic agent. 10. The peptide agent of claim 8, wherein X is a methoti-exate. 11. The peptide agent of claim 8, wherein X is selected fi'om the group consisting of the following compounds and their derivatives: doxorubicin, methotrexate, camptothecin, homocamptothecins, rliizoxins, dolistatins,. pachtaxol, and maytansinoids. 12. The peptide agent of claim 2, wherein Q is a somatostatin peptide. 13. The peptide agent of claim 2, wherein Q is a bombesin peptide. 14. The peptide agent of claim 2, wherein Z is D-Ser-Lys-D-Tyr-D-Tyr. 15. The peptide agent of claim 2, wherein Z is D-Ser-Lys-D-Tyr-D-Ser. 16. The peptide agent of claim 2, wherein Z is D-Ser-Ser-D-Lys-D-Ser. 17. The peptide agent of claim 2, wherein Z is D-Ser-Ser-D-Lys-Ser. IS. The peptide agent of claim 2, wherein Z is D-Ser-Nle-D-Tyr-D-Ser. 19. The peptide agent of claim 2, wherein Z is D-Ser-Pal-D-Tyr-D-Ser. 20. The peptide agent of claim 2, wherein Z is D-Ser-Thr-D-Tyr-D-Ser. 21. A method of treating a disease comprising administeiing to a subject suffering from said disease a therapeutically effective amount of a peptide agent having the fonnulk: X-Y-Z-Q, wherein: X is a cytotoxic agent or a therapeutic agent; Y is a peptide that increases the hydrophilic biodistribution of said agent, a hydrophilic polymer that includes a linlcer for X, or is omitted; 23. The method of claim 21, wherein Y is of the fomiula: U(V-V):,, wherein: U is D-Pro, L-Pro, D-4-OH-Pro, L-4-OH-Pro, Sar, or (NH.-(CH2)m-C00H) where m=2-10, inclusive, or is deleted; each V is independently selected fi-oni the group consisting of: D-Ser, L-Ser, D-Tlir, L^Thi, D-Gln, L-Gln, D-Asn, L-Asn, D-4-OH-Pro, and L-4-OH-Pro; and n is an integer from 1 to 50, inclusive. 24. The method of claim 23, wherem each V is independently D-Ser or L-Ser. 25. The method of claim 21, wherein Y is a hydrophihc polymer. 26. The method of claim 25, wherein Y is polyethylene glycol, polyvinyl acetate, or polyvinyl alcohol. 27. The method of claim 21, wherein X is a cytotoxic agent. 28. The method of claim 27, wherein X is an antimetabolic agent. 29. The method of claim 27, wherein X is a camptothecin. 30. The method of claim 27, wherein X is selected from the group consisting of the following compounds and their derivatives: doxoiiibicin, methotrexate, camptothecin, homocamptothecin, thiocolchicine, colchicine, combretastatins, combretastin A-4, rhizoxin, rhizoxin-d, dolistatins, paclitaxel, ansamitocin p3, and maytansinoids. 31. The method of claim 21, wherein Q is a somatostatin peptide. 32. The method of claim 21, wherein Q is a bombesin peptide. 33. The method of claim 21, wherein Z is Nle-D-T}T:-D-Ser. 34. The method of claim 21, wherein Z is Lys-D-Tyr-D-Ser. 35. The method of claim 21, wherein Z is Pal-D-Lys-D-Ser. 36. The method of claim 21, wherein Z is Thi'-D-T}a--D-Ser. 37. The method of claim 21, wherein the disease is selected fi*om the ; gi-Qup consisting of: tumors of the lung, breast, brain, eye, prostate, or colon; rumors of neuroendocrine origin; and angiogenic blood vessels. 38. A peptide agent having the fonnula: X-Y-Z-Q, wherein: X is a detectable label, a chelating group, or is omitted; Y is a peptide that increases the hydrophilic biodistribution of said agent, a hydrophilic polymer that includes a linker for X, or is omitted; Q is a peptide having biological activity; and Z is a linking peptide that, when bonded to Q at the N-temiinus or at a compatible side-chain amino gi'oup of Q, presences at least 50% of the said biological activity of Q, Z having the fomiula: C-E-F, wherein: C is Lys, Om, Dab, Dap, 4- NHa-Phe, Nle, Ser, hSer, Abu, Nva, D-4-OH-Pro, or L-4-OH-Pro, or is deleted; E and F are each independently selected from the group consisting of: D-Lys, D-T}a*, D-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-T}a', 3-5 diiodo-D-Tyr, 3-bromo-D-Tyi-, 3-5 dibromo-D-TvT, D-Asn, D-Asp, L-Asp, D-Glu, and L-Glu; and when C and E are Lys and D-T\a', respectively, F is not D-Tyi" or D-Lys. 39. The peptide agent of claim 38, wherein said peptide agent is attached to a detectable label. 40. The peptide agent of claim 39, wherein said peptide agent is indirectly attached to a detectable label. 41. The peptide agent of claim 39, wherein said peptide agent is directly attached to a detectable label. 42. The peptide agent of claim 39, wherein said detectable label is radioactive. 43. The peptide agent of claim 42, wherein said detectable label is an iodine, astatine, or bromine label that is attached to an amino acid of said peptide agent. 44. The peptide agent of claim 38, wherein X is a chelating gi'oup. 45. The peptide agent of claim 38, wherein X is omitted, and Y is lower acetylated, succinylated, maleinylated, or fumarylated. 46. The peptide agent of claim 38, wherein Y is a peptide sequence that increases the hydrophilic biodistiibution of said agent. 47. The peptide agent of claim 46, wherein Y is of the fomiiila: U(V-V)n, wherein: U is D-Pro, L-Pro, D-4-OH-Pro, L-4-OH-Pro, Sar, or (NH.-(CH2)m"C00H) where m=2-10, inclusive, or is deleted; each V is independently selected from the gi'oup consisting of: D-Ser, L-Ser, D-Tlir, L-Thr, D-Gln, L-Gln, D-Asn, L-Asn, D-4-OH-Pro, and L-4-OH-Pro; and n is an integer from 1 to 50, inclusive. 48. The peptide agent of claim 47, wherein each V is independently D- Ser, L-Ser, or D-Gln. i 49. The peptide agent of claim 38, wherein E is D-Tyr and F is D-Ser. 50. The peptide agent of claim 38, wherein Y is a hydrophilic polymer. 51. The peptide agent of claim 50, wherein Y is polyethyleneglycol, PHEA, or polyvinylalcohol. 52. The peptide agent of claim 38, wherein Q is a somatostatin peptide. 53. The peptide agent of claim 38, wherein Q is a bombesin peptide. 54. The peptide agent of claim 38, wherein Z is Lys-D-Tyi*-D-Ser. 55. The peptide agent of claim 38, wherein Z is Lys-D-Ser-D-Ser. 56. The peptide agent of claim 38, wherein Z is Nle-D-T}T-D-Ser. 57. A method of treating or diagnosing a disease comprising administering to a subject a therapeutically or diagnostically effective amount of a peptide agent having the fonnula: X-Y-Z-Q, wherein: X is a detectable label, a chelating group, or is omitted; Y is a peptide that increases the hydrophilic biodistribuiion of said agent, a hydrophilic polymer that includes a linker for X, or is omitted; Q is a peptide having biological activity; and Z is a linking peptide that, when bonded to Q at the N-terminus or at a compatible side-chain amino group of Q, preserves at least 50% of the said biological activity of Q, Z having the formula: C-E-F, wherein: C is Lys, Om, Dab, Dap, 4- NHs-Phe, Nle, Ser, hSer, Abu, Nva, D-4-OH-Pro, or L-4-OH-Pro, or is deleted; and E and F are each independently selected from the gi'onp :onsisting of: D-Lys, D-Tyr, D-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyr, 3-5 diiodo-D-Tyi-, D-Asn, D-Asp, L-Asp, D-Glu, and L-Glu; and when C and E are Lys and D-Tyr, respectively, F is not D-Tyi- or D-Lys. 58. The method of claim 57, wherein said peptide agent is attached to a detectable label. 59. The method of claim 58, wherein said peptide agent is indirectly attached to a detectable label. 60. The method of claim 58, wherein said peptide agent is directly attached to a detectable label. 61. The method of claim 58, wherein said detectable label is radioactive. 62. The method of claim 61, wherein said detectable label is an iodine .abel that is attached to an amino acid of said peptide agent. 63. The method of claim 57, wherein X is a chelating gi-oup. 64. The method of claim 57, wherein X is omitted, and Y isjower icetylated, succinylated, maleinylated or fumaiylated. 65. The method of claim 57, wherein Y is a peptide sequence that ncreases the hydrophilic biodistiibution of said agent. 66. The method of claim 65, wherein Y is of the fomiula: U(V-V)n, w^herein: U is D-Pro, L-Pro, D-4-OH-Pro, L-4-OH-Pro, Sar, or (NH.-CH2)in-C00H) where m=2-10, inclusive, or is deleted; each V is independently selected from the gi'oup consisting of: D-Ser, L-Ser, D-Thr, L-Thr, D-Gln, L-Gln, D-Asn, L-Asn, D-4-OH-Pro, and L-4-OH-Pro; and n is an integer from 1 to 50. inclusive. 67. The method of claim 66, wherein each V is independently D-Ser, L-Ser, orD-Gln, 6S. The method of claim 57, wherein Y is a hydropliilic polymer. 69. The method of claim 68, wherein Y is polyethyleneglycol, PHEA, or polyv'inylalcohol. 70. The method of claim 57, wherein Q is a somatostatin peptide. 71. The method of claim 57, wherein Q is a bombesin peptide, 72. The method of claim 57, wherein E is D-T>T and F is D-Ser. 73. The method of claim 57, wherein Z is Ly5-D-Tyi--D-Ser. 74. The method of claim 57, wherein Z is Lys-D-Ser-D-Ser. 75. The method of claim 57, wherein Z is Nle-D-Tyr-D-Ser. 76. The peptide agent of claim 2, wherein Q is bombesin and Z has the fomiula: E-F, wherein: E is D-Lys, D-Tyi", D-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-T)a, 3-5 diiodo-D-Tyr. 3-astatine-D-Tyi'- 3-5 astatine-D-Tyr_, 3-bromo-D-T>T, 3-5 dibromo-D-Tyr, D-Asn, L-Asn, D-Asp, L-Asp, D-Gln, or L-Gln; and F is D-Lys, D-Tyr, D-Ser, L-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyr, 3-5 diiodo-D-Tyr, 3-astatme-D-Tyi", 3-5 astatine-D-Tyr, 3-'bromo-D-Tyr, 3-5 dibromo-D-Tyr, D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Gln. '> 77. The method of claim 21, wherein Q is bombesin and Z has the fonnula: E-F, wherein: E is D-Lys, D-T)a\ D-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyr, 3-5 diiodo-D-Tyr, 3-astatine-D-Tyi-, 3-5 astatine-D-Tyr^ 3-bromo-D-Tyi-, ) 3-5 dibromo-D-Tyr, D-Asn, L-Asn, D-Asp, L-Asp, D-Gln, or L-Gln; and F is D-Lys, D-Tyi-, D-Ser, L-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyi-, 3-5 diiodo-D-Tyr, 3-astatine-D-Tyr, 3-5 astatine-D-Tyr, 3-bromo-D-Tyi\ 3-5 dibromo-D-Tyi", D-Asn, L-Asn, D-Asp, L-Asp, D-Glu, L-Glu, D-Gln, or L-Gln. 78. The peptide agent of claim 38, wherein Q is bombesin and Z has the fomiula: E-F, wherein: E and F are each independently selected from the gi'oup consisting of: D-Lys, D-Tyr, D-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-Tyr, 3-5 diiodo-D-Tyr, 3-bromo-D-Tyi', 3-5 dibromo-D-Tyr, D-Asn, D-Asp, L-Asp, D-Gln, and L-Glu. 79. The method of claim 57, wherein Q is bombesin and Z has the formula: E-F, wherein: E and F are each independently selected from the gi'oup consisting of: D-Lys, D-Tyr, D-Ser, D-4-OH-Pro, L-4-OH-Pro, 3-iodo-D-TyT, 3-5 diiodo-D-Tyr, 3-bromo-D-Tyr, 3-5 dibromo-D-Tyr, D-Asn, D-Asp, L-Asp, D-Glu, and L-Glu. 80. The peptide agent of claim 2, wherein Z is Lys-D-Tyi'-D-Ser. 81. The peptide agent of claim 2, wherein Z is Ser-D-Lys-D-Ser. 82. The peptide agent of claim 2, wherein Z is Ser-D-Lys-Ser. 83. The peptide agent of claim 2, wherein Z is Nle-D-Tyr-D-Ser. 84. The peptide agent of claim 2, wherein Z is Pal-D-Lys-D-Ser. 85. The peptide agent of claim 2, wherein Z is Thr-D-Tyr-D-Ser. 86. The method of claim 21, wherein Z is D-Ser-Lys-D-Tyr-D-Tyr. 87. The method of claim 21, wherein Z is D-Ser-Lys-D-Tyi*-D-Ser. SS. The method of claim 21, wherein Z is D-Ser-Ser-D-Lys-D-Ser. 89. The method of claim 21, wherein Z is D-Ser-Ser-D-Lys-Ser. 90. The method of claim 21, wherein Z is D-Ser-Nle-D-Tyr-D-Ser. 91. The method of claim 21, wherein Z is D-Ser-Pal-D-Tyr-D-Ser. 92. The method of claim 21, wherein Z is D-Ser-Thi'-D-Tyr-D-Ser. 93. The method of claim 21, wherein Z is Ser-D-Lys-Ser. 94. The method of claim 21, wherein Z is Ser-D-Lys-D-Ser. 95. The peptide agent of claim 4, wherein at least one Visa D-amino ' acid. 96. The method of claim 23, wherein at least one V is a D-amino acid. 97. The peptide agent of claim 47, wherein at least one V is a D-amino acid. 98. The method of claim 66, wherein at least one V is a D-amino acid. 99. The method of claim 37, wherein said tumor of neuroendocrine origin is carcinoid syndrome. 100. The peptide agent of claim 44. wherein said chelating group comprises an isotope of Lu, In, Y, or Sm. 101. The method of claim 63, wherein said chelating group comprises an isotope of Lu, In, Y, or Sm. 102. A peptide agent substantially as herein described with reference to me accompanying drawings. 103. A method of treating a disease substantially as herein described with reference to the accompanying drawings.

Documents:

0817-chenp-2004 claims-duplicate.pdf

0817-chenp-2004 descripition(completed)-duplicate.pdf

0817-chenp-2004 drawings-duplicate.pdf

817-chenp-2004 abstract.pdf

817-chenp-2004 claims.pdf

817-chenp-2004 correspondence others.pdf

817-chenp-2004 correspondence po.pdf

817-chenp-2004 description (complete).pdf

817-chenp-2004 petition.pdf

817-chenp-2004 power of attorney.pdf

817-chenp-2004-claims.pdf

817-chenp-2004-correspondnece-others.pdf

817-chenp-2004-correspondnece-po.pdf

817-chenp-2004-description(complete).pdf

817-chenp-2004-drawings.pdf

817-chenp-2004-form 1.pdf

817-chenp-2004-form 18.pdf

817-chenp-2004-form 3.pdf

817-chenp-2004-form 5.pdf

817-chenp-2004-pct.pdf