Patent ID: 7238341

Claim:
A method of making an MR imaging agent, said method comprising: a) reacting a peptide having an N-terminal amine functional group with a linker-subunit moiety to form a modified peptide having a C-terminal amine functional group and said N-terminal amine functional group; b) covalently attaching a linker moiety to the C-terminal amine functional group and to the N-terminal amine functional group to form a precursor MR imaging agent; c) converting the precursor MR imaging agent to the MR imaging agent; wherein converting the precursor MR imaging agent to the MR imaging agent comprises: (d) reacting the precursor MR imaging agent with a precursor chelate moiety to form a covalent bond between the precursor chelate moiety and the linker moiety of the precursor MR imaging agent; (e) reacting the covalently linked precursor MR imaging agent and precursor chelate moiety to produce a plurality of carboxylate moieties; and (f) complexing a paramagnetic metal ion to the plurality of carboxylate moieties to produce the MR imaging agent; wherein the linker-subunit moiety is: wherein the precursor chelate moiety is selected from the group consisting of: wherein LG is a leaving group selected from the group consisting of —OH, a pentafluorophenol (Pfp) moiety, a N-hydroxysuccinimide (NHS) moiety, a N-hydroxysulfosuccinimide salt (NHSS) moiety, a 2-thioxothiazolidin-1-yl moiety, a hydroxybenozotriazole (HBT) moiety, and a halide, and wherein each R, independently, is an O − or an O − precursor selected from the group consisting of OH, —O-Me, O-Et, O-tBu, O-benzyl, and O-allyl.