Evaluation of novel cationic 99mTc(I)-tricarbonyl complexes as potential radiotracers for myocardial perfusion imaging |
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Authors: | He Zhengjie Hsieh Wen-Yuan Kim Young-Seung Liu Shuang |
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Institution: | aSchool of Health Sciences, Purdue University, West Lafayette, IN 47907-2051, USA |
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Abstract: | This report describes the evaluation of three cationic 99mTc(I)–tricarbonyl complexes — 99mTc(CO)3(L)]+ (L=N-methoxyethyl-N,N-bis2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (ME-PNP), N-15-crown-5)-2-yl]-N,N-bis2-(bis(3-ethoxypropyl)phosphino)ethyl]amine (15C5-PNP) and N-18-crown-6)-2-yl]-N,N-bis2-(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 99mTc(I)–tricarbonyl complexes. Among the three radiotracers evaluated in this study, 99mTc(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 99mTc(CO)3(15C5-PNP)]+ is 2.5 times better than that of 99mTc-sestamibi at 30 min postinjection. 99mTc(CO)3(15C5-PNP)]+ is almost identical to 99mTcN-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 99mTc(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 99mTc(CO)3(15C5-PNP)]+ has a much better liver clearance profile than 99mTc-sestamibi and might give clinically useful images of the heart as early as 30 min postinjection. 99mTc(CO)3(15C5-PNP)]+ is a very promising candidate for more preclinical evaluations in various animal models. |
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Keywords: | Cationic 99mTc(I)–tricarbonyl complexes Radiopharmaceuticals PNP bisphosphines |
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