Evaluation of novel cationic 99mTc(I)-tricarbonyl complexes as potential radiotracers for myocardial perfusion imaging.

摘要

This report describes the evaluation of three cationic (99m)Tc(I)-tricarbonyl complexes--[(99m)Tc(CO)(3)(L)](+) (L=N-methoxyethyl-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (ME-PNP), N-[15-crown-5)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (15C5-PNP) and N-[18-crown-6)-2-yl]-N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (18C6-PNP))--as potential radiotracers for myocardial perfusion imaging. Biodistribution, imaging and metabolism studies were performed using Sprague-Dawley rats. It was found that bisphosphine ligands have a significant impact on the biodistribution characteristics and clearance kinetics of their cationic (99m)Tc(I)-tricarbonyl complexes. Among the three radiotracers evaluated in this study, [(99m)Tc(CO)(3)(15C5-PNP)](+) has a very high initial heart uptake and is retained in the rat myocardium for >2 h. It also shows rapid clearance from the liver and lungs. The heart/liver ratio of [(99m)Tc(CO)(3)(15C5-PNP)](+) is approximately 2.5 times better than that of (99m)Tc-sestamibi at 30 min postinjection. [(99m)Tc(CO)(3)(15C5-PNP)](+) is almost identical to (99m)TcN-DBODC5 with respect to heart uptake, heart/lung ratio and heart/liver ratio. Results from metabolism studies show that there is no significant metabolism for [(99m)Tc(CO)(3)(15C5-PNP)](+) in the urine, but it does show a small metabolite peak (<10%) in the radio high-performance liquid chromatography chromatogram of the feces sample at 120 min postinjection. Results planar imaging studies demonstrate that [(99m)Tc(CO)(3)(15C5-PNP)](+) has a much better liver clearance profile than (99m)Tc-sestamibi and might give clinically useful images of the heart as early as 30 min postinjection. [(99m)Tc(CO)(3)(15C5-PNP)](+) is a very promising candidate for more preclinical evaluations in various animal models.