Novel 3+1 mixed-ligand Technetium-99m complexes carrying dipeptides as monodentate ligands

Abstract

Novel mixed ligand oxotechnetium complexes of the type [(TcO)-Tc-99m(SSS)(SR)], in which the SR monodentate ligand is derived from dipeptides gly-gly, phe-gly and ala-gly, have been synthesized. These complexes, which have a molecular weight above 300, a lipophilic moiety, [TcO(SSS)](+), and an ionizable group separated from the lipophilic moiety by a spacer, have been obtained in 70-95% radiochemical yield. These compounds were prepared using Tc-99m-tartrate as the precursor and Sn2+ as the reducing agent. The identity of the [(TcO)-Tc-99m(SSS)(SR)] complexes has been established by HPLC comparison with the analogous oxorhenium complexes. The nature of the monodentate co-ligand strongly affects the stability of the Tc-99m-complexes and their biodistribution. Complex 3b is the most stable in vitro presenting the highest blood clearance, a high liver uptake and a selective hepatobiliary excretion (54.5% ID at 15 min post-injection, and 69.3% ID at 60 min post injection). The results obtained show that 3b have reasonable stability and in vivo properties that may be useful for peptide labeling. (C) 2004 Elsevier Inc. All rights reserved.