Claims
- 1. A reagent for preparing a scintigraphic imaging agent, said reagent comprising a specific binding peptide having from about three to about 100 amino acids and being covalently linked to a radiolabel-binding moiety that forms an electrically neutral complex when bound to a radioisotope.
- 2. The reagent of claim 1, wherein the peptide and the moiety are covalently linked through from about one to about 20 amino acids.
- 3. The reagent of claim 1 wherein the radioisotope is technetium-99m.
- 4. The reagent of claim 1 wherein the peptide is selected from the group consisting of peptides having the amino acid sequences:
- formyl-MLF
- (VGVAPG).sub.3 amide
- (VPGVG).sub.4 amide
- RALVDTLKFVTQAEGAKamide (SEQ ID No.:1)
- RALVDTEFKVKQEAGAKamide (SEQ ID No.:2)
- PLARITLPDFRLPEIAIPamide (SEQ ID No.:3)
- GQQHHLGGAKAGDV (SEQ ID No.:4)
- PLYKKIIKKLLES (SEQ ID No.:5)
- LRALVDTLKamide (SEQ ID No.:6)
- GGGLRALVDTLKamide (SEQ ID No.:7)
- GGGLRALVDTLKFVTQAEGAKamide (SEQ ID No.:8)
- GGGRALVDTLKALVDTLamide (SEQ ID No.:9)
- GHRPLDKKREEAPSLRPAPPPISGGGYR (SEQ ID No.:10)
- PSPSPIHPAHHKRDRRQamide (SEQ ID No.:11)
- GGGF.sub.D.Cpa.YW.sub.D KTFTamide (SEQ ID No.:12) ##STR6## (SYNRGDSTC).sub.3 -TSEA GGGLRALVDTLKamide (SEQ ID No.:14)
- GCGGGLRALVDTLKamide (SEQ ID No.:15)
- GCYRALVDTLKFVTQAEGAKamide (SEQ ID No.:16) and
- GC(VGVAPG).sub.3 amide.
- 5. A reagent for preparing a scintigraphic imaging agent comprising:
- a) at least two specific binding peptides, each having an amino acid sequence of from about1 three to about 100 amino acids;
- b) at least one radiolabel binding moiety capable of forming an electrically neutral complex with a radioisotope; and
- c) a polyvalent linking moiety covalently linked to the peptides and to the radiolabel binding moiety, thereby forming a multimer,
- wherein the molecular weight of the reagent is less than about 20,000 daltons.
- 6. The reagent of claim 5 wherein the polyvalent linking moiety is bis-succinimidylmethylether, 4-(2,2-dimethylacetyl)benzoic acid, N-[2-(N',N'-bis(2-succinimidoethyl)aminoethyl)]-N.sup.6,N.sup.9 -bis(2-methyl-2-mercaptopropyl)-6,9-diazanonanamide, tris(succinimidylethyl)amine or a derivative thereof.
- 7. A scintigraphic imaging agent comprising the reagent of claim 1, wherein the moiety is bound to a radiolabel.
- 8. The agent of claim 7, wherein the radiolabel is technetium-99m.
- 9. A process of preparing the reagent of claim 1, wherein the peptide is chemically synthesized in vitro.
- 10. The process of claim 9, wherein the peptide is synthesized by solid phase peptide synthesis.
- 11. A reagent for preparing a scintigraphic imaging agent, said reagent comprising a specific binding peptide having from about 3 to about 100 amino acids and being covalently linked to a radiolabel-binding moiety of formula: ##STR7## wherein X=H or a protecting group;
- (amino acid)=any amino acid;
- and wherein the moiety forms an electrically neutral complex when bound to a radioisotope.
- 12. The reagent of claim 11, wherein (amino acid) is glycine and X is an acetamidomethyl protecting group.
- 13. The reagent of claim 11, wherein the peptide and the moiety are covalently linked through from about one to about 20 amino acids.
- 14. The reagent of claim 11 wherein the radioisotope is technetium-99m.
- 15. The reagent of claim 11, wherein the peptide is selected from the group consisting of:
- formyl-MLF
- (VGVAPG).sub.3 amide
- (VPGVG).sub.4 amide
- RALVDTLKFVTQAEGAKamide (SEQ ID No.:1)
- RALVDTEFKVKQEAGAKamide (SEQ ID No.:2)
- PLARITLPDFRLPEIAIPamide (SEQ ID No.:3)
- GQQHHLGGAKAGDV (SEQ ID No.:4)
- PLYKKIIKKLLES (SEQ ID No.:5)
- LRALVDTLKamide (SEQ ID No.:6)
- GGGLRALVDTLKamide (SEQ ID No.:7)
- GGGLRALVDTLKFVTQAEGAKamide (SEQ ID No.:8)
- GGGRALVDTLKALVDTLamide (SEQ ID No.:9)
- GHRPLDKKREEAPSLRPAPPPISGGGYR (SEQ ID No.:10)
- PSPSPIHPAHHKRDRRQamide (SEQ ID No.:11)
- GGGF.sub.D.Cpa.YW.sub.D KTFTamide (SEQ ID No.:12) ##STR8## (SYNRGDSTC).sub.3 -TSEA GGGLRALVDTLKamide (SEQ ID No.:14)
- GCGGGLRALVDTLKamide (SEQ ID No.:15)
- GCYRALVDTLKFVTQAEGAKamide (SEQ ID No.:16) and
- GC(VGVAPG).sub.3 amide.
- 16. The reagent of claim 5, wherein the radiolabel-binding moiety is selected from the group consisting of: ##STR9## wherein X=H or a protecting group;
- (amino acid)=any amino acid; ##STR10## wherein X=H or a protecting group;
- (amino acid)=any amino acid; ##STR11## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;
- each (pgp).sup.S is independently a thiol protecting group or H;
- m, n and p are independently 2 or 3;
- A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof; and ##STR12## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;
- m, n and p are independently 2 or 3;
- A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;
- V=H or --CO-peptide;
- R'=H or peptide;
- and wherein when V=H, R'=peptide and when R'=H, V=--CO-peptide.
- 17. The reagent of claim 16, wherein the polyvalent linking moiety is bis-succinimidylmethylether, 4-(2,2-dimethylacetyl)benzoic acid, N-[2-(N',N'-bis(2-succinimido-ethyl)aminoethyl)]-N.sup.6,N.sup.9 -bis(2-methyl-2-mercaptopropyl)-6,9-diazanonanamide, tris(succinimidylethyl)amine or a derivative thereof.
- 18. A scintigraphic imaging agent comprising the reagent of claim 11, wherein the moiety is bound to a radiolabel.
- 19. The agent of claim 18, wherein the radiolabel is technetium-99m.
- 20. A process of preparing the reagent of claim 11, wherein the peptide is chemically synthesized in vitro.
- 21. The process of claim 20, wherein the peptide is synthesized by solid phase peptide synthesis.
- 22. A reagent for preparing an scintigraphic imaging agent, said reagent comprising a specific binding peptide having from about 3 to about 100 amino acids, and being covalently linked to a radiolabel-binding moiety, wherein the moiety forms an electrically neutral complex when bound to a radioisotope, said moiety having a formula selected from the group consisting of: ##STR13## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;
- each (pgp).sup.S is independently a thiol protecting group or H;
- m, n and p are independently 2 or 3;
- A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof; and ##STR14## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 ;
- m, n and p are independently 2 or 3;
- A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;
- V=H or --CO-peptide;
- R'=H or peptide;
- and wherein when V=H, R'=peptide and when R'=H, V=--CO-peptide.
- 23. The reagent of claim 22, wherein the peptide and the moiety are covalently linked through from about one to about 20 amino acids.
- 24. The reagent of claim 22, wherein the radioisotope is technetium-99m.
- 25. The reagent of claim 22, wherein the peptide is selected from the group consisting of:
- formyl-MLF
- (VGVAPG).sub.3 amide
- (VPGVG).sub.4 amide
- RALVDTLKFVTQAEGAKamide (SEQ ID No.:1)
- RALVDTEFKVKQEAGAKamide (SEQ ID No.:2)
- PLARITLPDFRLPEIAIPamide (SEQ ID No.:3)
- GQQHHLGGAKAGDV (SEQ ID No.:4)
- PLYKKIIKKLLES (SEQ ID No.:5)
- LRALVDTLKamide (SEQ ID No.:6)
- GGGLRALVDTLKamide (SEQ ID No.:7)
- GGGLRALVDTLKFVTQAEGAKamide (SEQ ID No.:8)
- GGGRALVDTLKALVDTLamide (SEQ ID No.:9)
- GHRPLDKKREEAPSLRPAPPPISGGGYR (SEQ ID No.:10)
- PSPSPIHPAHHKRDRRQamide (SEQ ID No.:11)
- GGGF.sub.D.Cpa.YW.sub.D KTFTamide (SEQ ID No.:12) ##STR15## (SYNRGDSTC).sub.3 -TSEA GGGLRALVDTLKamide (SEQ ID No.:14)
- GCGGGLRALVDTLKamide (SEQ ID No.:15)
- GCYRALVDTLKFVTQAEGAKamide (SEQ ID No.:16) and
- GC(VGVAPG).sub.3 amide.
- 26. A scintigraphic imaging agent comprising the reagent of claim 22, wherein the moiety is bound to a radiolabel.
- 27. The agent of claim 26, wherein the radiolabel is technetium-99m.
- 28. A process of preparing the reagent of claim 22, wherein the peptide is chemically synthesized in vitro.
- 29. The process of claim 28, wherein the peptide is synthesized by solid phase peptide synthesis.
- 30. A composition comprising an .epsilon.-amino group of a N-.alpha.-protected lysine attached to a radiolabel-binding moiety having a formula selected from the group consisting of: ##STR16## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 but if X=H, one R=Y;
- (pgp).sub.N =an amine protecting group or H;
- each (pgp).sup.S is independently a thiol protecting group or H;
- m, n and p are independently 2 or 3;
- X=H or --A--COOH, but if X=H, one R=Y and (pgp).sub.N is not H;
- Y=--A--COOH;
- A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof; ##STR17## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 but if Z=H, one R=Y;
- each (pgp).sub.N is an amine protecting group or H;
- each (pgp).sup.S is independently a thiol protecting group or H;
- m, n and p are independently 2 or 3;
- Z=H or --A--CH(V)NH(pgp).sub.2.sup.N, but if Z=H, one R=Y;
- Y=--A--CH(V)NH(pgp).sub.2.sup.N ;
- A=linear lower alkyl, cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;
- V=H or COOH;
- and wherein if (pgp).sub.1.sup.N and V are H, then (pgp).sup.S is not H and if (pgp).sup.S and V are H, then (pgp).sup.N is not H, and if V is H, (pgp).sub.1.sup.N is not H; and ##STR18## wherein each R is independently H, CH.sub.3 or C.sub.2 H.sub.5 and one R=Y;
- each (pgp).sup.N is an amine protecting group or H;
- each (pgp).sup.S is independently a thiol protecting group or H;
- m, n and p are independently 2 or 3;
- Y=--A--CH(V)NH(pgp).sub.2.sup.N ;
- A=linear or cyclic lower alkyl, aryl, heterocyclyl, a combination thereof, or a substituted derivative thereof;
- V=H or COOH;
- and wherein if (pgp).sub.2.sup.N and V are H, then (pgp).sup.S is not H and if (pgp).sup.S and V are H, then (pgp).sub.2.sup.N is not H, and at least one (pgp).sub.1.sup.N moiety is not H.
- 31. A composition comprising [N-.epsilon.-(N.sup.9 -t-butoxycarbonyl)-N.sup.6,N.sup.9 -bis[2-methyl-2-(triphenylmethylthio)propyl]-6,9-diazanonanoyl)-N-.alpha.-Fmoc-lysine.
Parent Case Info
This application claims priority to International Application PCT/US93/03687, filed Apr. 19, 1993, which is a continuation-in-part of U.S. Ser. No. 07/871,282, filed Apr. 30, 1992, incorporated by reference herein.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US93/03687 |
4/19/1993 |
|
|
2/9/1995 |
2/9/1995 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO93/21962 |
11/11/1993 |
|
|
US Referenced Citations (20)
Foreign Referenced Citations (3)
Number |
Date |
Country |
0174853 |
Mar 1986 |
EPX |
0188256 |
Jul 1986 |
EPX |
90306428 |
May 1990 |
EPX |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
871282 |
Apr 1992 |
|