Synthesis of 18F-labeled Novel Phosphonium cations as PET Myocardial Perfusion Imaging Agents: Pilot Imaging Studies

Abstract

The development of myocardial perfusion imaging (MPI) agents has been motivated because coronary artery disease has been one of the leading causes of death worldwide since the 1960s. Several positron emission tomography (PET) MPI agents were developed, and 18F-labeled phosphonium cations were reported actively among them. In this study, we synthesized novel 18F-labeled phosphonium cations, (5-[18F]fluoropentyl)diphenyl( pyridin-2-yl)phosphonium and (2-(2-[18F]fluoroethoxy)ethyl)diphenyl(pyridin-2-yl)phosphonium, and evaluated potential as MPI agents. Two labeled compounds were synthesized via nucleophilic substitution reactions of 18F-fluoride with the appropriate tosylate precursor in the presence of Kryptofix 2.2.2 and K2CO3. MicroPET studies were performed in normal rats to evaluate in vivo distribution of radiolabeled phosphonium cations for 60 min. The radiolabeled compounds were synthesized with 5%–10% yield. The radiochemical purity of labeled compounds was > 98% by analytical HPLC, and the specific activity was > 11.8 GBq/μmol. The result of microPET studies of these labeled compounds in rats showed intense uptake in the myocardium at 30 and 60 min. The results suggest that these 18F-labeled novel phosphonium cations would have potential as promising candidates for myocardial perfusion imaging.