Synthesis and evaluation of [18F]-fluoromethyl triphenylphosphonium cation as a novel mitochondria-specific positron emission tomography tracer

Abstract We developed a radiosynthesis of the voltage sensitive tracer [ 18 F]-fluoromethyltriphenylphosphonium cation ([ 18 F]-FTPMP), giving high yield (30–34%, decay-corrected), radiochemical purity (>99%) and specific activity (about 760 GBq/μmol). [ 18 F]-FTPMP had suitable lipophilicity (logP = 0.91 ± 0.03) and high in vivo / vitro stability. Biodistribution studies showed that [ 18 F]-FTPMP had high heart uptake (>7%ID/g from 10 min to 120 min postinjection) and rapid clearance from the background. Clear cardiac images were obtained at different time periods, and the infarction areas could be detected sensitively with small-animal PET. The autoradiography and myocardial membrane potential studies confirmed the mitochondria specific of [ 18 F]-FTPMP in rat myocardia. These excellent pharmacokinetic properties suggest [ 18 F]-FTPMP is a promising mitochondria-specific tracer for clinical PET imaging of myocardial diseases associated with mitochondrial dysfunction.