Metal radionuclide labeled proteins for diagnosis and therapy

Claim 2

Radionuclide metal chelates, where the chelating agent is a N,N'-bis-mercaptoacetyl ω,ω-1-diamino aliphatic carboxylic acid or amine of at least four carbon atoms or derivative thereof.

Claim 3

A compound of the formula: wherein: M is a metal or metal oxide radionuclide ion capable of being chelated; one of Z 1 ', Z 2 ', Z 3 ' or Z 4 ' is R'CW'(HNV')Y', and the others are H 2 or =0; R' is an aliphatic divalent radical of from 1 to 6 carbon atoms and 0 to 2 heteroatoms; Y' is hydroxyl, an oxy salt, an ester group, -NH2, -NHNH 2 , or a polypeptide of at least about 1000 molecular weight; V' is of the formula R'CW'; W' is =NH or =0, with the proviso that W is H 2 when Y' is -NH 2 ; X' is a bond, methylene or CHZ 4 ';

Claim 4

A compound of the formula: wherein: M is a metal or metal oxide radionuclide ion capable of being chelated; one of Z 1 ', Z 2 ', Z 3 ' or Z 4 ' is R'CW'(HNV')Y', and the others are H 2 or =0; R' is an aliphatic divalent radical of from 1 to 6 carbon atoms and 0 to 2 heteroatoms; Y' is hydroxyl, an oxy salt, an ester group, -NH2, -NHNH 2 , or a polypeptide of at least about 1000 molecular weight; V' is of the formula R'CW'; W' is =NH or =0, with the proviso that W is H 2 when Y' is -NH 2 ; X' is a bond, methylene or CHZ 4 ';

Claim 5

A compound according to Claim 2, wherein Y' is a polypeptide.

Claim 6

4 . A compound according to Claim 3, wherein Y' is an immunoglobulin or specific binding fragment thereof.

Claim 7

. A compound of the formula: wherein: one of Z 1 , Z 2 , Z 3 or Z 4 is RCW(HNV) Y, and the others are H 2 or =O; R is a divalent organic radical of from 1 to 6 carbon atoms and 0 to 2 heteroatoms; W is =NH or =0, with the proviso that W is H 2 when Y is -NH 2 ; V is the same or different from RCW and comes within the definitions of RCW; n is 0 or 1; T is a removable protective group, hydrogen, an alkali metal ion, or the two T's may be taken together to define a polyvalent metal radionuclide; Y is hydroxyl, an oxy salt, an organic oxy compound forming an ester, -NH 2 , -NHNH 2 , or a polypeptide of at least two amino acids; X is a bond, methylene, or CHZ 4 ; and the A's are the same or different and are hydrogen or lower alkyl of from 1 to 6 carbon atoms.

Claim 8

. A compound of the formula: wherein: one of Z 1 , Z 2 , Z 3 or Z 4 is RCW(HNV) Y, and the others are H 2 or =O; R is a divalent organic radical of from 1 to 6 carbon atoms and 0 to 2 heteroatoms; W is =NH or =0, with the proviso that W is H 2 when Y is -NH 2 ; V is the same or different from RCW and comes within the definitions of RCW; n is 0 or 1; T is a removable protective group, hydrogen, an alkali metal ion, or the two T's may be taken together to define a polyvalent metal radionuclide; Y is hydroxyl, an oxy salt, an organic oxy compound forming an ester, -NH 2 , -NHNH 2 , or a polypeptide of at least two amino acids; X is a bond, methylene, or CHZ 4 ; and the A's are the same or different and are hydrogen or lower alkyl of from 1 to 6 carbon atoms.

Claim 9

6 . A compound according to Claim 5, wherein X is a bond.

Claim 10

A method for preparing a radiolabeled ligand or receptor polypeptide which comprises: combining in an aqueous medium a compound of the formula according to Claim 4, wherein Y is an ester group capable of forming an amide or amidine link with said polypeptide or NH 2 or NHNH 2 , with the proviso that when Y is -NH 2 , said polypeptide has an oxo-group as a result of glycol cleavage of a sugar bound to said polypeptide and said combining is under reductive amination conditions; wherein said compound forms a stable covalent link to said polypeptide with the substantial absence of unchelated radionuclide.

Claim 11

A method for preparing a radiolabeled ligand or receptor polypeptide which comprises: combining in an aqueous medium a compound according to Claim 11, wherein T is an alkali metal ion and Y is said polypeptide and a metal radionuclide in a reduced chelated exchangeable form; whereby said radionuclide becomes chelated by said compound; and washing said radionuclide containing compound tc remove unchelated radionuclide bound to said compound .