US 5,620,675 A · Radioactive peptides

Abstract

This invention relates to therapeutic reagents and peptides, radiodiagnostic reagents and peptides, and methods for producing label radiodiagnostic agents. Specifically, the invention relates to linear peptide derivatives and analogs of somatostatin, and embodiments of such peptides radiolabeled with a radioisotope, as well as methods and kits for making, radiolabeling and using such peptides for radiodiagnostic and radiotherapeutic purposes. The invention specifically relates to linear peptide derivatives and analogues of somatostatin radiolabeled with technetium-99m and uses thereof as scintigraphic imaging agents. The invention so specifically relates to liner peptide derivatives and analogues of somatostatin radiolabeled with cytotoxic radioisotopes such as rhenium-186 (.sup.186 Re) and rhenium-188 (.sup.188 Re) for use as radiotherapeutic agents. Methods and kits for making, radiolabeling and using such peptides diagnostically and therapeutically in a mammalian body are also provide.

Claims68

Dependent claims

A composition of matter that is linear somatostatin receptor-binding peptide reagent having the formula:

X.sup.1 -A.sup.1 A.sup.2 -B.sup.1 B.sup.2 B.sup.3 B.sup.4 -C.sup.1 C.sup.2 -X.sup.2
wherein
X.sup.1 and X.sup.2 are each independently hydrophilic moieties wherein X.sup.1 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 polyoxyanion, and X.sup.2 is a 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;
A.sup.1, A.sup.2 and C.sup.1 are each independently a lipophilic D- or L-amino acid, or S-alkylated cysteine, penicillamine, homocysteine or homohomocysteine;
B.sup.1 is D- or L-Phe, or D- or L-Tyr, or D- or L-Nal, or Ain or substituted derivatives thereof;
B.sup.2 is D- or L-Trp or substituted derivatives thereof;
B.sup.3 is D- or L-Lys, or Hly, Achxa, Amf, Aec, Apc, Aes, Aps or substituted derivatives thereof;
B.sup.4 and C.sup.2 are each independently D- or L-Thr, Ser, Val, Phe, Ile, Abu, Nle,
Leu, Nva, Nal or Aib or substituted derivatives thereof;
and wherein the somatostatin receptor-binding peptide reagent does not comprise a radiolabel chelating moiety.

7 more elements

A composition of matter that is a linear somatostatin receptorbinding peptide reagent having the formula:

X.sup.1 -A.sup.1 A.sup.2 -B.sup.1 B.sup.2 B.sup.3 B.sup.4 -C.sup.1 C.sup.2 -X.sup.2
wherein
X.sup.1 is H, lower alkyl or substituted alkyl, aryl or substituted aryl, alkanoyl or substituted alkanoyl, aroyl or substituted aroyl, or a hydrophilic moiety;
A.sup.1, A.sup.2 and C.sup.1 are each independently a lipophilic D- or L-amino acid, or S-alkylated cysteine, penicillamine, homocysteine or homohomocysteine;
B.sup.1 is D- or L-Phe, or D- or L-Tyr, or D- or L-Nal, or Ain or substituted derivatives thereof;
B.sup.2 is D- or L-Trp or substituted derivatives thereof;
B.sup.3 is D- or L-Lys, or Hly, Achxa, Amf, Aec, Apc, Aes, Aps or substituted derivatives thereof;
B.sup.4 and C.sup.2 are each independently D- or L-Thr, Ser, Val, Phe, Ile, Abu, Nle, Leu, Nva, Nal or Aib or substituted derivatives thereof;
X.sup.2 is --COOR.sup.9, --CH.sub.2 OH, CH.sub.2 COOR.sup.9,or --CON(R.sup.9).sub.2, where each R.sup.9 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.sup.1, B.sup.2, B.sup.3 or B.sup.4 of the peptide and wherein the radiolabel binding moiety is capable of binding Tc-99m, Re-186 or Re-188.

7 more elements

Dependencies are inferred from the claim text.

Radioactive peptides

Life of this patent

Radioactive peptides

Life of this patent

Abstract

Claims68