Synthesis, characterization and pre-clinical evaluation of ~(99m)Tc-tricarbonyl complexes as potential myocardial perfusion imaging agents

摘要

Myocardial perfusion imaging is an established Nuclear Medicine investigation. Current myocardial perfusion imaging agents sestamibi and tetrofosmin have number of drawbacks; low heart uptake coupled with uptake into the surrounding tissues leads to a poorer image quality. There is a need for continued research into designing and evaluating potentially superior myocardial imaging agents.Tri-carbonyl-technetium and rhenium complexes were prepared by combination with mono-dentate and bi-dentate ligands. Complexes were characterized by HPLC, MAS, nuclear magnetic resonance, infrared, single-crystal X-ray diffraction and partition coefficient determinations. ~(99m)Tc(CO)_3 complexes were administered intravenously to Sprague Dawley rats, and tissue distribution studies were carried out at 15min and 1h p.i. Radiochemical purity was assessed as >90%. 1-10-phenanthroline, 2,2'-bipyridine and imidazole complexes gave the highest heart uptake. The percentage injected dose per gram (n = 3) at 1 h for 1-10-phenanthroline/imidazole was blood 0.21 +-0.01, heart 1.12 +-0.11, kidney 3.61 +-1.13, liver 0.62 +-0.06, lung 0.28 +-0.12, spleen 0.24 +-0.05, small intestine contents 1.87 +-0.92; and for 2,2'-bipyridine /imidazole was blood 0.23 +-0.02, heart 1.07 +-0.18, kidney 3.31 +-1.28, liver 0.56 +-0.09, lung 0.14 +-0.02, spleen 0.2 +-0.1, small intestine content 1.05 +-0.48.Further investigation to evaluate more complexes based on 1,10-phenanthroline, 2,2'-bipyridine and imidazole derivatives could potentially lead to agents with an increased heart uptake and faster clearance from the liver and gastrointestinal tract.