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

• Published in: Nuclear medicine and biology Vol. 31; no. 1; pp. 139 - 146
• Main Authors: Fernandes, Célia, Patrício, Luciana, Moreira, Rui, Cantinho, Guilhermina, Pena, Helena, Campello, Paula C., Santos, Isabel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2004
• Subjects: 3+1 approach; 99mTc; Animals; Biodistribution studies; Dipeptides; Dipeptides - chemistry; Dipeptides - pharmacokinetics; Drug Stability; Female; Isotope Labeling; Ligands; Metabolic Clearance Rate; Mice; Organ Specificity; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Technetium - chemistry; Technetium - pharmacokinetics; Tissue Distribution; 3+1 approach; Dipeptides; 99mTc; Re; Biodistribution studies
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/S0969-8051(03)00129-X

Novel mixed ligand oxotechnetium complexes of the type [ 99mTcO(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 99mTc-tartrate as the precursor and Sn 2+ as the reducing agent. The identity of the [ 99mTcO(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 99mTc-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.