Synthesis, characterization and pre-clinical evaluation of 99mTc-tricarbonyl complexes as potential myocardial perfusion imaging agents

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. Tc-99m(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 1h for 1-10-phenanthroline/imidazole was blood 0.210.01, 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.