WO1995003330B1 - Somatostatin derivatives and their radiolabelled products - Google Patents
Somatostatin derivatives and their radiolabelled productsInfo
- Publication number
- WO1995003330B1 WO1995003330B1 PCT/US1994/008335 US9408335W WO9503330B1 WO 1995003330 B1 WO1995003330 B1 WO 1995003330B1 US 9408335 W US9408335 W US 9408335W WO 9503330 B1 WO9503330 B1 WO 9503330B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- reagent
- somatostatin receptor
- amino acid
- peptide
- substituted derivatives
- Prior art date
Links
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical class C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 title claims abstract 5
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract 24
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 8
- 229940056501 Technetium 99m Drugs 0.000 claims abstract 7
- GKLVYJBZJHMRIY-OUBTZVSYSA-N technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 claims abstract 7
- 239000003795 chemical substances by application Substances 0.000 claims abstract 4
- 239000012216 imaging agent Substances 0.000 claims abstract 4
- 230000003439 radiotherapeutic Effects 0.000 claims abstract 4
- WUAPFZMCVAUBPE-NJFSPNSNSA-N 188Re Chemical compound [188Re] WUAPFZMCVAUBPE-NJFSPNSNSA-N 0.000 claims abstract 3
- WUAPFZMCVAUBPE-IGMARMGPSA-N rhenium-186 Chemical compound [186Re] WUAPFZMCVAUBPE-IGMARMGPSA-N 0.000 claims abstract 3
- 229960000553 Somatostatin Drugs 0.000 claims abstract 2
- 102000005157 Somatostatin Human genes 0.000 claims abstract 2
- 108010056088 Somatostatin Proteins 0.000 claims abstract 2
- 230000001472 cytotoxic Effects 0.000 claims abstract 2
- 231100000433 cytotoxic Toxicity 0.000 claims abstract 2
- 230000027455 binding Effects 0.000 claims 19
- 102000011096 Somatostatin receptor family Human genes 0.000 claims 17
- 108050001286 Somatostatin receptor family Proteins 0.000 claims 17
- 150000001413 amino acids Chemical group 0.000 claims 10
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 8
- 150000001412 amines Chemical class 0.000 claims 8
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 6
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims 6
- 235000001014 amino acid Nutrition 0.000 claims 6
- 239000000203 mixture Substances 0.000 claims 6
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 5
- 239000003638 reducing agent Substances 0.000 claims 5
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 4
- 239000004472 Lysine Substances 0.000 claims 4
- 150000001720 carbohydrates Chemical group 0.000 claims 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 125000005647 linker group Chemical group 0.000 claims 4
- 150000002772 monosaccharides Chemical class 0.000 claims 4
- 229920001542 oligosaccharide Polymers 0.000 claims 4
- 150000002482 oligosaccharides Polymers 0.000 claims 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N L-serine Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 3
- -1 Nal Chemical compound 0.000 claims 3
- IUTCEZPPWBHGIX-UHFFFAOYSA-N tin(2+) Chemical compound [Sn+2] IUTCEZPPWBHGIX-UHFFFAOYSA-N 0.000 claims 3
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims 2
- FLICZDVBYUMMAS-UHFFFAOYSA-N 4-(2-methylpropanoyl)benzoic acid Chemical compound CC(C)C(=O)C1=CC=C(C(O)=O)C=C1 FLICZDVBYUMMAS-UHFFFAOYSA-N 0.000 claims 2
- QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 claims 2
- 229940044173 Iodine-125 Drugs 0.000 claims 2
- 150000008575 L-amino acids Chemical class 0.000 claims 2
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims 2
- VVNCNSJFMMFHPL-GSVOUGTGSA-N L-penicillamine Chemical compound CC(C)(S)[C@H](N)C(O)=O VVNCNSJFMMFHPL-GSVOUGTGSA-N 0.000 claims 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims 2
- 229960005190 Phenylalanine Drugs 0.000 claims 2
- 239000004473 Threonine Substances 0.000 claims 2
- 125000003435 aroyl group Chemical group 0.000 claims 2
- 239000011230 binding agent Substances 0.000 claims 2
- 125000001589 carboacyl group Chemical group 0.000 claims 2
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 claims 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims 2
- CWYNVVGOOAEACU-UHFFFAOYSA-N fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims 2
- 229910001448 ferrous ion Inorganic materials 0.000 claims 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims 2
- 238000002372 labelling Methods 0.000 claims 2
- 229960001639 penicillamine Drugs 0.000 claims 2
- 125000003107 substituted aryl group Chemical group 0.000 claims 2
- 239000004474 valine Substances 0.000 claims 2
- FJZFPQVTPJCIAT-UHFFFAOYSA-N 1-[bis(2,5-dioxopyrrolidin-1-yl)methoxy-(2,5-dioxopyrrolidin-1-yl)methyl]pyrrolidine-2,5-dione Chemical group O=C1CCC(=O)N1C(N1C(CCC1=O)=O)OC(N1C(CCC1=O)=O)N1C(=O)CCC1=O FJZFPQVTPJCIAT-UHFFFAOYSA-N 0.000 claims 1
- 229940006110 Gallium-67 Drugs 0.000 claims 1
- ZCYVEMRRCGMTRW-RNFDNDRNSA-N I-131 Chemical compound [131I] ZCYVEMRRCGMTRW-RNFDNDRNSA-N 0.000 claims 1
- HAJIWLPYCZPZSP-UHFFFAOYSA-N N-[2-[bis[2-[(2-chloroacetyl)amino]ethyl]amino]ethyl]-2-chloroacetamide Chemical compound ClCC(=O)NCCN(CCNC(=O)CCl)CCNC(=O)CCl HAJIWLPYCZPZSP-UHFFFAOYSA-N 0.000 claims 1
- XVSZNYOHTAKUGI-UHFFFAOYSA-N N-[acetamido(diacetamidomethoxy)methyl]acetamide Chemical compound CC(=O)NC(NC(C)=O)OC(NC(C)=O)NC(C)=O XVSZNYOHTAKUGI-UHFFFAOYSA-N 0.000 claims 1
- 239000007983 Tris buffer Substances 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- JCXGWMGPZLAOME-AKLPVKDBSA-N bismuth-212 Chemical compound [212Bi] JCXGWMGPZLAOME-AKLPVKDBSA-N 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- RYGMFSIKBFXOCR-AKLPVKDBSA-N copper-67 Chemical compound [67Cu] RYGMFSIKBFXOCR-AKLPVKDBSA-N 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- KBQHZAAAGSGFKK-NJFSPNSNSA-N dysprosium-165 Chemical compound [165Dy] KBQHZAAAGSGFKK-NJFSPNSNSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- UIWYJDYFSGRHKR-NJFSPNSNSA-N gadolinium-159 Chemical compound [159Gd] UIWYJDYFSGRHKR-NJFSPNSNSA-N 0.000 claims 1
- GYHNNYVSQQEPJS-OIOBTWANSA-N gallium-67 Chemical compound [67Ga] GYHNNYVSQQEPJS-OIOBTWANSA-N 0.000 claims 1
- GYHNNYVSQQEPJS-YPZZEJLDSA-N gallium-68 Chemical compound [68Ga] GYHNNYVSQQEPJS-YPZZEJLDSA-N 0.000 claims 1
- GYHNNYVSQQEPJS-NJFSPNSNSA-N gallium-72 Chemical compound [72Ga] GYHNNYVSQQEPJS-NJFSPNSNSA-N 0.000 claims 1
- KJZYNXUDTRRSPN-OUBTZVSYSA-N holmium-166 Chemical compound [166Ho] KJZYNXUDTRRSPN-OUBTZVSYSA-N 0.000 claims 1
- 238000003384 imaging method Methods 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- ZCYVEMRRCGMTRW-AHCXROLUSA-N iodine-123 Chemical compound [123I] ZCYVEMRRCGMTRW-AHCXROLUSA-N 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- OHSVLFRHMCKCQY-NJFSPNSNSA-N lutetium-177 Chemical compound [177Lu] OHSVLFRHMCKCQY-NJFSPNSNSA-N 0.000 claims 1
- 238000010647 peptide synthesis reaction Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 239000012217 radiopharmaceutical Substances 0.000 claims 1
- 230000002799 radiopharmaceutical Effects 0.000 claims 1
- KZUNJOHGWZRPMI-AKLPVKDBSA-N samarium-153 Chemical compound [153Sm] KZUNJOHGWZRPMI-AKLPVKDBSA-N 0.000 claims 1
- SIXSYDAISGFNSX-NJFSPNSNSA-N scandium-47 Chemical compound [47Sc] SIXSYDAISGFNSX-NJFSPNSNSA-N 0.000 claims 1
- 239000007790 solid phase Substances 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- NAWDYIZEMPQZHO-NJFSPNSNSA-N ytterbium-175 Chemical compound [175Yb] NAWDYIZEMPQZHO-NJFSPNSNSA-N 0.000 claims 1
- VWQVUPCCIRVNHF-OUBTZVSYSA-N yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 claims 1
- 238000000163 radioactive labelling Methods 0.000 abstract 2
- 230000001225 therapeutic Effects 0.000 abstract 1
Abstract
This invention relates to therapeutic reagents and peptides, radiodiagnostic reagents and peptides, and methods for producing labelled radiodiagnostic agents. Specifically, the invention relates to linear peptide derivatives and analogs of somatostatin, and embodiments of such peptides radiolabelled with a radioisotope, as well as methods and kits for making, radiolabelling and using such peptides for radiodiagnostic and radiotherapeutic purposes. The invention specifically relates to linear peptide derivatives and analogues of somatostatin radiolabelled with technetium-99m and uses thereof as scintigraphic imaging agents. The invention also specicically relates to linear peptide derivatives and analogues of somatostatin radiolabelled with cytotoxic radioisotopes such as rhenium-186 (186Re) and rhenium-188 (188Re) for use as radiotherapeutic agents. Methods and kits for making, radiolabelling and using such peptides diagnostically and therapeutically in a mammalian body are also provided.
Claims
1. A composition of matter that is somatostatin receptor-binding peptide reagent having the formula:
X'-A^-B^B^-W-X2 wherein X1 and X2 are each independently hydrophilic moieties;
A1, A2 and C1 are each independently a lipophilic D- or L-amino acid, or S-alkylated cysteine, penicillamine, homocysteine or homohomocysteine;
B1 is D- or L-Phe, or D- or L-Tyr, or D- or L-Nal, or Ain or substituted derivatives thereof;
B2 is D- or L-Trp or substituted derivatives thereof;
B3 is D- or L-Lys, or Hly, Achxa, Amf, Aec, Ape, Aes, Aps or substituted derivatives thereof;
B4 is D- or L-Thr, Ser, Val, Phe, He, Abu, Nle, Leu, Nva, Nal or Aib or substituted derivatives thereof; and
C2 is D- or L-Thr, Ser, Val, Phe, He, Abu, Nle, Leu, Nva, Nal or Aib or substituted derivatives thereof.
2. The peptide of Claim 1 wherein X1 is an amino acid, or a peptide having an amino acid sequence of no more than 10 residues, or a monosaccharide, or an oligosaccharide comprising 10 or fewer saccharide units, or a poly (N-carboxy alky l)amine, or a polyoxyanion, and X2 is a poly(N- carboxyalkyl)amine or polyoxyanion, or an amino acid, or a peptide having an amino acid sequence of no more than 10 residues (including peptides wherein the carboxyl group of the carboxyl-terminal amino acid is reduced to an alcohol), or a monosaccharide or an oligosaccharide comprising 10 or fewer saccharide units.
3. The somatostatin receptor-binding peptide of Claim 1 wherein B1 is phenylalanine or tyrosine, B2 is D-tryptophan, B3 is lysine and B4 is threonine or valine.
4. The composition of matter of Claim 1 further comprising a polyvalent linking moiety that is covalently linked to a multiplicity of the somatostatin receptor-binding peptides to form a multimeric polyvalent somatostatin receptor binding agent, wherein the molecular weight of the multimeric polyvalent somatostatin receptor binding agent is less than about
53 20,000 daltons.
5. The reagent of Claim 4 wherein the polyvalent linking moiety is bis- succinimidylmethylether, 4-(2,2-dimethylacetyl)benzoic acid, N-(2-(N',N'-b -s(2- succinimidoethyl)aminoethyl))-N6,N9-bj'-s(2-methyl-2-mercaptopropyl)-6,9- diazanonanamide, tra(succinimidylethyl)amine tris(2-cMoroacetamidoethyl)amine, l,2-bw-(2-(chloroacetamido) ethoxy)ethane, tπ's(acetamidoethyl)amine, bis- acetamidomethyl ether, bw-acetamidoethyl ether, α,e-b 5-acetyllysine, lysine and 1,8- bw-acetamido-3,6-dioxa-octane, or a derivative thereof.
6. The composition of matter of Claim 1 wherein the somatostatin receptor-binding peptide is chemically synthesized in vitro.
7. The composition of matter of Claim 18 wherein the somatostatin receptor-binding peptide is synthesized by solid phase peptide synthesis.
8. Use of the somatostatin receptor binding peptide of Claim 1 for preparing a medicament for alleviating a somatostatin-related disease in an animal, wherein the medicament comprises a therapeutically effective amount of the somatostatin receptor binding peptide of Claim 1.
9. A use according to Claim 8 wherein the animal is a human.
10. A composition of matter that is a somatostatin receptor-binding peptide reagent having the formula:
X1-A1A2-B1B2B3B4-C1C2-X2 wherein X1 is H, lower alkyl or substituted alkyl, aryl or substituted aryl, alkanoyl or substituted alkanoyl, aroyl or substituted aroyl, or a hydrophilic moiety;
A1, A2 and C1 are each independently a lipophilic D- or L-amino acid, or 5-alkylated cysteine, penicillamine, homocysteine or homohomocy steine ; B1 is D- or L-Phe, or D- or L-Tyr, or D- or L-Νal, or Ain or substituted derivatives thereof;
B2 is D- or L-Trp or substituted derivatives thereof;
B3 is D- or L-Lys, or Hly, Achxa, Amf, Aec, Ape, Aes, Aps or substituted derivatives thereof; B4 is D- or L-Thr, Ser, Nal, Phe, He, Abu, Νle, Leu, Νva, Νal or
54 or Aib or substituted derivatives thereof; C2 is D- or L-Thr, Ser, Val, Phe, He, Abu, Nle, Leu, Nva, Nal or Aib or substituted derivatives thereof; X2 is -COOR9, -CH2OH, CH2COOR9, or -CON(R9)2, where each R9 is independently H, lower linear or cyclic alkyl or substituted derivatives thereof or substituted with a hydrophilic moiety; and wherein the somatostatin receptor binding peptide is covalently linked to a radiolabel-binding moiety, wherein the radiolabel-binding moiety is not covalently linked to the moieties B\ B2, B3, B4 or B4 of the peptide.
11. The reagent of Claim 10 wherein X1 is a an amino acid, or a peptide having an amino acid sequence of no more than 10 residues, or a monosaccharide, or an oligosaccharide comprising 10 or fewer saccharide units, or a poly(N-carboxyalkyl)amine, or a polyoxyanion and X2 is a poly(N- carboxyalkyl)amine or a polyoxyanion, or an amino acid, or an amino acid, or a peptide having an amino acid sequence of no more than 10 residues, or a monosaccharide, or an oligosaccharide comprising 10 or fewer saccharide units.
12. The somatostatin receptor-binding peptide of Claim 10 wherein B1 is phenylalanine or tyrosine, B2 is D-tryptophan, B3 is lysine and B4 is threonine or valine.
13. The reagent of Claim 10 wherein the reagent further comprises a polyvalent linking moiety covalently linked to a multiplicity of the somatostatin receptor binding peptides and also covalently linked to a multiplicity of radiolabel-binding moieties to comprise a reagent for preparing a multimeric polyvalent somatostatin receptor binding reagent, wherein the molecular weight of the multimeric polyvalent somatostatin receptor binding reagent is less than about 20,000 daltons.
14. The reagent of Claim 13 wherein the polyvalent linking moiety is tø-succinimidylmethylether, 4-(2,2-dimethylacetyl)benzoic acid, N-(2-(N',N'- bt 2-succinimidoemyl)aminoethyl))-N6,N9-bw(2-methyl-2-mercaptopropyl)-6,9- d iazanonanamid e , tr**,s ( suc c inimidy l ethy l ) ami ne tris ( 2 - chloroacetamidoethyl)amine, 1 ,2-b«-(2-(chloroacetamido) ethoxy)ethane, tπ'j(acetamidoethyl)amine, bz'-s-acetamidomethyl ether, bw-acetamidoethyl ether, cx,e-bw-acetyllysine, lysine and l,8-tø-acetamido-3,6-dioxa-octane, or a derivative thereof.
15. A scintigraphic imaging agent comprising the reagent of Claim 10
55 radiolabeled with technetium-99m.
16. A scintigraphic imaging agent comprising the reagent of Claim 10 radiolabeled with indium-Ill, gallium-67 or gallium-68.
17. A scintigraphic imaging agent comprising the somatostatin receptor binding peptide of Claim 1 radiolabeled with iodine-123 or iodine-125.
18. A radiotherapeutic agent comprising the reagent of Claim 10 radiolabeled with a cytotoxic radioisotope selected from the group consisting of scandium-47, copper-67, gallium-72, yttrium-90, samarium-153, gadolinium-159, dysprosium- 165, holmium- 166, ytterbium- 175, lutetium-177, rhenium- 186, rhenium- 188, and bismuth-212.
19. A radiotherapeutic agent comprising the somatostatin receptor binding peptide of Claim 1 radiolabeled with iodine- 125, iodine-131 or astatine-131.
20. A complex formed by reacting the reagent of Claim 10 with technetium-99m in the presence of a reducing agent.
21. The complex of Claim 20 , wherein the reducing agent is selected from the group consisting of a dithionite ion, a stannous ion and a ferrous ion.
22. A complex formed by labeling the reagent of Claim 10 with technetium-99m by ligand exchange of a prereduced technetium-99m complex.
23. A composition of matter comprising the reagent of Claim 10 and a stannous ion.
24. A kit for preparing a radiopharmaceutical preparation, said kit comprising a sealed vial containing a predetermined quantity of the reagent of Claim 10 and a sufficient amount of reducing agent to label the reagent with technetium- 99m.
25. A method for labeling a reagent according to Claim 10 comprising reacting the reagent with technetium-99m in the presence of a reducing agent.
26. The method of Claim 25, wherein the reducing agent is selected from the group consisting of a dithionite ion, a stannous ion and a ferrous ion.
27. Use of the reagent of Claim 15 for preparing a medicament for imaging a site within a mammalian body, wherein the medicament comprises an effective diagnostic amount of the reagent of Claim 15.
56
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP50535995A JP3601827B2 (en) | 1993-07-21 | 1994-07-21 | Somatostatin derivatives and their radiolabels |
| US08/586,670 US6241965B1 (en) | 1993-07-21 | 1994-07-21 | Somatostatin derivatives and their radiolabelled products |
| AT94925686T ATE237637T1 (en) | 1993-07-21 | 1994-07-21 | SOMATOSTATIN DERIVATIVES AND THEIR RADIOM-LABELED PRODUCTS |
| DK94925686T DK0804481T3 (en) | 1993-07-21 | 1994-07-21 | Somatostatin derivatives and their radiolabelled products |
| AU75506/94A AU684823B2 (en) | 1993-07-21 | 1994-07-21 | Somatostatin derivatives and their radiolabelled products |
| DE69432530T DE69432530T2 (en) | 1993-07-21 | 1994-07-21 | SOMATOSTATIN DERIVATIVES AND THEIR RADIO-MARKED PRODUCTS |
| EP94925686A EP0804481B1 (en) | 1993-07-21 | 1994-07-21 | Somatostatin derivatives and their radiolabelled products |
| CA002167678A CA2167678C (en) | 1993-07-21 | 1994-07-21 | Radioactive peptides |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/095,760 | 1993-07-21 | ||
| US08/095,760 US5620675A (en) | 1992-06-23 | 1993-07-21 | Radioactive peptides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1995003330A1 WO1995003330A1 (en) | 1995-02-02 |
| WO1995003330B1 true WO1995003330B1 (en) | 1995-03-16 |
Family
ID=22253472
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1994/008335 WO1995003330A1 (en) | 1993-07-21 | 1994-07-21 | Somatostatin derivatives and their radiolabelled products |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US5620675A (en) |
| EP (1) | EP0804481B1 (en) |
| JP (1) | JP3601827B2 (en) |
| AT (1) | ATE237637T1 (en) |
| AU (1) | AU684823B2 (en) |
| CA (1) | CA2167678C (en) |
| DE (1) | DE69432530T2 (en) |
| DK (1) | DK0804481T3 (en) |
| ES (1) | ES2197169T3 (en) |
| WO (1) | WO1995003330A1 (en) |
| ZA (1) | ZA945367B (en) |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5985240A (en) * | 1989-08-09 | 1999-11-16 | Rhomed Incorporated | Peptide radiopharmaceutical applications |
| US5443816A (en) * | 1990-08-08 | 1995-08-22 | Rhomed Incorporated | Peptide-metal ion pharmaceutical preparation and method |
| US5965107A (en) * | 1992-03-13 | 1999-10-12 | Diatide, Inc. | Technetium-99m labeled peptides for imaging |
| US5849261A (en) * | 1991-02-08 | 1998-12-15 | Diatide, Inc. | Radiolabeled vasoactive intestinal peptides for diagnosis and therapy |
| US7238340B1 (en) * | 1991-11-27 | 2007-07-03 | Cis Bio International | Monoamine, diamide, thiol-containing metal chelating agents |
| US5997844A (en) * | 1991-02-08 | 1999-12-07 | Diatide, Inc. | Technetium-99m labeled peptides for imaging |
| US5443815A (en) * | 1991-11-27 | 1995-08-22 | Diatech, Inc. | Technetium-99m labeled peptides for imaging |
| US5783170A (en) * | 1991-11-27 | 1998-07-21 | Diatide, Inc. | Peptide-metal chelate conjugates |
| US5508020A (en) * | 1992-06-05 | 1996-04-16 | Diatech, Inc. | Technetium-99M labeled peptides for imaging |
| US6017512A (en) * | 1992-06-23 | 2000-01-25 | Diatide, Inc. | Radiolabeled peptides |
| US5716596A (en) * | 1992-06-23 | 1998-02-10 | Diatide, Inc. | Radioactively labeled somatostatin-derived peptides for imaging and therapeutic uses |
| US5620675A (en) * | 1992-06-23 | 1997-04-15 | Diatech, Inc. | Radioactive peptides |
| AU707040B2 (en) * | 1993-06-23 | 1999-07-01 | Cis Bio International | Monoamine, diamide, thiol-containing metal chelating agents |
| US5932189A (en) * | 1994-07-29 | 1999-08-03 | Diatech, Inc. | Cyclic peptide somatostatin analogs |
| ATE234639T1 (en) * | 1994-05-02 | 2003-04-15 | Diatide Inc | TECHNETIUM-99M LABELED IMAGE-FORMING AGENTS |
| US5891418A (en) * | 1995-06-07 | 1999-04-06 | Rhomed Incorporated | Peptide-metal ion pharmaceutical constructs and applications |
| CA2247430A1 (en) * | 1996-02-27 | 1997-09-04 | Mallinckrodt Medical, Inc. | Use of labelled cck-b receptor ligands for the detection and localization of malignant human tumors |
| US6331285B1 (en) | 1996-06-05 | 2001-12-18 | Palatin Technologies, Inc. | Structurally determined cyclic metallo-constructs and applications |
| US6355613B1 (en) | 1996-07-31 | 2002-03-12 | Peptor Limited | Conformationally constrained backbone cyclized somatostatin analogs |
| FI965181A (en) * | 1996-12-20 | 1998-06-21 | Map Medical Technologies Oy | Polyalcohol peptide derivatives |
| EP1056773A2 (en) * | 1998-02-11 | 2000-12-06 | Resolution Pharmaceuticals Inc. | Angiogenesis targeting molecules |
| US6465613B1 (en) | 1998-11-19 | 2002-10-15 | Tulane University | Hydrophilic somatostatin analogs |
| US6314314B1 (en) | 1999-01-14 | 2001-11-06 | Seth J. Karp | Method for locating an internal bleeding site in a human body |
| US20020102208A1 (en) | 1999-03-01 | 2002-08-01 | Paul Chinn | Radiolabeling kit and binding assay |
| MY133346A (en) * | 1999-03-01 | 2007-11-30 | Biogen Inc | Kit for radiolabeling ligands with yttrium-90 |
| US7067111B1 (en) * | 1999-10-25 | 2006-06-27 | Board Of Regents, University Of Texas System | Ethylenedicysteine (EC)-drug conjugates, compositions and methods for tissue specific disease imaging |
| GB0018891D0 (en) | 2000-08-01 | 2000-09-20 | Novartis Ag | Organic compounds |
| JP5448284B2 (en) * | 2000-06-02 | 2014-03-19 | ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム | Ethylenedicysteine (EC) -drug conjugate |
| US7385025B2 (en) | 2000-12-19 | 2008-06-10 | Palatin Technologies, Inc. | Metallopeptide compounds |
| EP1283216A1 (en) * | 2001-08-10 | 2003-02-12 | Mallinckrodt Inc. | Somatostatin analogues binding to all somatostatin receptor subtypes and their use |
| WO2003028527A2 (en) | 2001-09-21 | 2003-04-10 | The Administrators Of The Tulane Educational Fund | Diagnostic or therapeutic somatostatin or bombesin analog conjugates and uses thereof |
| AU2002365258A1 (en) * | 2001-10-12 | 2003-09-02 | University Of Vermont And State Agricultural College | Binding peptides specific for the extracellular domain of erbb2 and uses therefor |
| WO2003057214A1 (en) * | 2001-12-28 | 2003-07-17 | Somatocor Pharmaceuticals, Inc. | Imidazolidin-2,4-dione derivatives as non-peptide somatostatin receptor ligands |
| DK1487493T3 (en) * | 2002-03-01 | 2010-05-25 | Univ Tulane | Conjugates of cytotoxic agents and biologically active peptides |
| EP1369134A1 (en) * | 2002-06-05 | 2003-12-10 | Bracco Imaging S.p.A. | New agents for magnetic imaging method |
| IL150384A0 (en) * | 2002-06-24 | 2002-12-01 | Peptor Ltd | Radiolabelled somatostatin analogs backbone cyclized through metal complexation |
| US7709613B2 (en) * | 2002-11-18 | 2010-05-04 | Albert Einstein College Of Medicine Of Yeshiva University | Rhenium-188 and rhenium-186 for treatment of tumors expressing a Na+/I− symporter |
| JP2006522100A (en) * | 2003-03-10 | 2006-09-28 | バイオジェン アイデック インク | Thiol-mediated drug binding to targeting peptides |
| WO2005018682A2 (en) | 2003-08-20 | 2005-03-03 | The Regents Of The University Of California | Somatostatin analogs with inhibitory activity to growth hormone release |
| US9050378B2 (en) * | 2003-12-10 | 2015-06-09 | Board Of Regents, The University Of Texas System | N2S2 chelate-targeting ligand conjugates |
| WO2005123144A2 (en) * | 2004-01-20 | 2005-12-29 | Board Of Regents, The University Of Texas System | System and method for an automated synthesis of gallium-68 generator-based radiopharmaceutical agents |
| US20060024229A1 (en) * | 2004-07-29 | 2006-02-02 | Seth Karp | Method and product for locating an internal bleeding site |
| GB0421308D0 (en) * | 2004-09-24 | 2004-10-27 | Amersham Plc | Enzyme inhibitor imaging agents |
| FR2876033B1 (en) * | 2004-10-01 | 2008-12-05 | Inst Nat Sante Rech Med | USE OF VCAM-1 LIGANDS FOR THE DETECTION AND / OR TREATMENT OF CARDIOVASCULAR DISEASES |
| US7833513B2 (en) | 2004-12-03 | 2010-11-16 | Rhode Island Hospital | Treatment of Alzheimer's Disease |
| US8758723B2 (en) | 2006-04-19 | 2014-06-24 | The Board Of Regents Of The University Of Texas System | Compositions and methods for cellular imaging and therapy |
| US9308198B2 (en) | 2006-09-08 | 2016-04-12 | Rhode Island Hospital | Treatment, prevention, and reversal of alcohol-induced brain disease |
| KR101922515B1 (en) | 2006-09-08 | 2019-02-20 | 로드아일랜드하스피틀 | Treatment, prevention, and reversal of alcohol-induced liver disease |
| US10925977B2 (en) | 2006-10-05 | 2021-02-23 | Ceil>Point, LLC | Efficient synthesis of chelators for nuclear imaging and radiotherapy: compositions and applications |
| US20080167544A1 (en) * | 2006-12-01 | 2008-07-10 | Cold Spring Diagnostics, Inc. | Compositions And Methods For Locating An Internal Bleeding Site |
| WO2012159107A1 (en) | 2011-05-19 | 2012-11-22 | Rhode Island Hospital | Inhibition of renal fibrosis |
| WO2015099094A1 (en) | 2013-12-27 | 2015-07-02 | 国立大学法人東京医科歯科大学 | Method for diagnosis of alzheimer's disease and frontotemporal lobar degeneration, diagnostic agent, therapeutic agent, and screening method for said agents |
Family Cites Families (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL7607987A (en) | 1975-08-08 | 1977-02-10 | Merck & Co Inc | METHOD FOR PREPARING PEPTIDES. |
| CA1083143A (en) | 1976-01-02 | 1980-08-05 | Nedumparambil A. Abraham | Carba derivatives of somatostatin and process therefor |
| CA1107273A (en) | 1978-05-19 | 1981-08-18 | Chester A. Meyers | Somatostatin analogs having a substituted tryptophyl residue in position eight |
| NZ195303A (en) | 1979-10-31 | 1984-10-19 | Merck & Co Inc | Cyclic hexapeptide somatostatin analogues,and pharmaceutical compositions |
| US4235886A (en) * | 1979-10-31 | 1980-11-25 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
| US4444690A (en) * | 1982-02-25 | 1984-04-24 | University Patents, Inc. | Technetium chelates |
| US4472509A (en) * | 1982-06-07 | 1984-09-18 | Gansow Otto A | Metal chelate conjugated monoclonal antibodies |
| DE3379657D1 (en) * | 1982-12-06 | 1989-05-24 | Merck & Co Inc | Dicyclic hexapeptides, processes for their preparation and pharmaceutical compositions containing them |
| US4485101A (en) * | 1983-10-11 | 1984-11-27 | Administrators Of The Tulane Educational Fund | Peptides |
| US4608251A (en) * | 1984-11-09 | 1986-08-26 | Pitman-Moore, Inc. | LHRH analogues useful in stimulating anti-LHRH antibodies and vaccines containing such analogues |
| HUT42101A (en) * | 1985-01-07 | 1987-06-29 | Sandoz Ag | Process for preparing stomatostatine derivatives and pharmaceutical compositions containing such compounds |
| US5077195A (en) * | 1985-03-01 | 1991-12-31 | Board Of Reagents, The University Of Texas System | Polypeptides complementary to peptides or proteins having an amino acid sequence or nucleotide coding sequence at least partially known and methods of design therefor |
| US4725577A (en) | 1985-04-25 | 1988-02-16 | Administrators Of The Tulane Educational Fund | Biologically active lysine containing octapeptides |
| US4650787A (en) | 1985-04-25 | 1987-03-17 | Schally Andrew Victor | Biologically active octapeptides |
| US4611054A (en) * | 1985-04-29 | 1986-09-09 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
| US4612366A (en) * | 1985-06-17 | 1986-09-16 | Merck & Co., Inc. | Cyclic hexapeptide somatostatin analogs |
| US4904642A (en) * | 1985-09-12 | 1990-02-27 | The Administrators Of The Tulane Educational Fund | Therapeutic somatostatin analogs |
| US4877868A (en) * | 1986-03-12 | 1989-10-31 | Neorx Corporation | Radionuclide antibody coupling |
| US4853371A (en) * | 1986-06-17 | 1989-08-01 | The Administrators Of The Tulane Educational Fund | Therapeutic somatostatin analogs |
| US4871717A (en) * | 1987-01-07 | 1989-10-03 | Administrators Of The Tulane Educational Fund | Peptides |
| WO1988007382A2 (en) | 1987-04-02 | 1988-10-06 | Centocor Cardiovascular Imaging Partners, L.P. | Method for labelling antibodies with a metal ion |
| US5073541A (en) * | 1987-11-18 | 1991-12-17 | Administrators Of The Tulane Educational Fund | Treatment of small cell lung cancer with somatostatin analogs |
| WO1989010759A1 (en) | 1988-04-29 | 1989-11-16 | Mallinckrodt, Inc. | Diaminedithiol chelating agents for radiopharmaceuticals |
| US5084442A (en) * | 1988-09-06 | 1992-01-28 | Hoffmann-La Roche Inc. | Cyclic growth hormone releasing factor analogs and method for the manufacture thereof |
| GB9111199D0 (en) * | 1991-05-23 | 1991-07-17 | Sandoz Ltd | Improvements in or relating to organic compounds |
| MY106120A (en) | 1988-12-05 | 1995-03-31 | Novartis Ag | Peptide derivatives. |
| US4971477A (en) | 1988-12-22 | 1990-11-20 | Total Containment, Inc. | Secondary contained fluid supply system |
| US5196510A (en) * | 1988-12-29 | 1993-03-23 | Cytogen Corporation | Molecular recognition units |
| CA2012115C (en) * | 1989-03-15 | 2001-07-03 | Biomeasure, Inc. | Iodinated somatostatins |
| US5095111A (en) | 1989-03-17 | 1992-03-10 | The John Hopkins University | Thiolactone bifunctional chelating agents for diagnostic and therapeutic products |
| WO1990012811A1 (en) * | 1989-04-26 | 1990-11-01 | The Administrators Of The Tulane Educational Fund | Linear somatostatin analogs |
| HU219336B (en) | 1989-07-20 | 2001-03-28 | Novartis Ag | Process for producing peptide derivatives and pharmaceutical compositions comprising such compounds and diagnostic unit containing such compounds |
| US5443816A (en) | 1990-08-08 | 1995-08-22 | Rhomed Incorporated | Peptide-metal ion pharmaceutical preparation and method |
| IL97459A0 (en) * | 1990-03-09 | 1992-06-21 | Hybritech Inc | Trifunctional antibody-like compounds as a combined diagnostic and therapeutic agent |
| TW212184B (en) * | 1990-04-02 | 1993-09-01 | Takeda Pharm Industry Co Ltd | |
| US5178025A (en) | 1990-08-31 | 1993-01-12 | Innovative Medical Engineering, Inc. | Tiltable lift seat devices |
| US5965107A (en) | 1992-03-13 | 1999-10-12 | Diatide, Inc. | Technetium-99m labeled peptides for imaging |
| US5561220A (en) | 1991-02-08 | 1996-10-01 | Diatech, Inc. | Technetium-99m labeled peptides for imaging inflammation |
| WO1992013554A1 (en) | 1991-02-08 | 1992-08-20 | Biomeasure, Inc. | Method of treating benign and malignant proliferative skin disease |
| WO1992013572A1 (en) | 1991-02-08 | 1992-08-20 | Diatech, Inc. | TECHNETIUM-99m LABELED POLYPEPTIDES FOR IMAGING |
| US5552525A (en) | 1991-02-08 | 1996-09-03 | Diatech Inc. | Technetium-99m labeled peptides for imaging inflammation |
| US5443815A (en) * | 1991-11-27 | 1995-08-22 | Diatech, Inc. | Technetium-99m labeled peptides for imaging |
| JP3407260B2 (en) | 1991-08-09 | 2003-05-19 | コルベツク，ヴインフリート | Lanthionine cross-linked peptide |
| US5225180A (en) * | 1991-09-10 | 1993-07-06 | Diatech, Inc. | Technetium-99m labeled somatostatin-derived peptides for imaging |
| DE69231586T2 (en) | 1992-01-03 | 2001-07-19 | Rhomed Inc | PHARMACEUTICAL APPLICATIONS BASED ON PEPTIDE METAL IONS |
| CA2129033A1 (en) | 1992-02-05 | 1993-08-19 | Leon Lyle | Radiolabelled peptide compounds |
| DK0630265T3 (en) | 1992-03-13 | 2003-06-30 | Diatide Inc | Technetium-99m labeled peptides for imaging inflammation |
| US5508020A (en) | 1992-06-05 | 1996-04-16 | Diatech, Inc. | Technetium-99M labeled peptides for imaging |
| ES2150945T3 (en) | 1992-05-21 | 2000-12-16 | Diatide Inc | PEPTIDES MARKED WITH TECNETIO-99M TO OBTAIN IMAGES OF THROMBS. |
| US5620675A (en) * | 1992-06-23 | 1997-04-15 | Diatech, Inc. | Radioactive peptides |
| US5871711A (en) * | 1992-06-23 | 1999-02-16 | Diatide, Inc. | Radioactively-labeled somatostatin-derived peptides for imaging and therapeutic uses |
| US5716596A (en) | 1992-06-23 | 1998-02-10 | Diatide, Inc. | Radioactively labeled somatostatin-derived peptides for imaging and therapeutic uses |
| ATE222264T1 (en) | 1992-10-02 | 2002-08-15 | Diatide Inc | MULTIMERIC MULTIPURPOSE ACTIVES AGAINST THROMBOSIS |
| EP0720621B1 (en) | 1993-06-23 | 2001-02-07 | Diatide, Inc. | Radiolabeled somatostatin-derived peptides for imaging and therapeutic uses |
-
1993
- 1993-07-21 US US08/095,760 patent/US5620675A/en not_active Expired - Fee Related
-
1994
- 1994-07-21 AU AU75506/94A patent/AU684823B2/en not_active Ceased
- 1994-07-21 ZA ZA945367A patent/ZA945367B/en unknown
- 1994-07-21 WO PCT/US1994/008335 patent/WO1995003330A1/en active IP Right Grant
- 1994-07-21 AT AT94925686T patent/ATE237637T1/en not_active IP Right Cessation
- 1994-07-21 ES ES94925686T patent/ES2197169T3/en not_active Expired - Lifetime
- 1994-07-21 DK DK94925686T patent/DK0804481T3/en active
- 1994-07-21 EP EP94925686A patent/EP0804481B1/en not_active Expired - Lifetime
- 1994-07-21 US US08/586,670 patent/US6241965B1/en not_active Expired - Fee Related
- 1994-07-21 DE DE69432530T patent/DE69432530T2/en not_active Expired - Fee Related
- 1994-07-21 JP JP50535995A patent/JP3601827B2/en not_active Expired - Fee Related
- 1994-07-21 CA CA002167678A patent/CA2167678C/en not_active Expired - Fee Related
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