Synthesis and Evaluation of 18F-Labeled Fluoroalkyl Triphenylphosphonium Salts as Mitochondrial Voltage Sensors in PET Myocardial Imaging

Abstract

We have previously reported that radiolabeled phosphonium cations accumulate in the mitochondria down a transmembrane potential gradient. We present an optimized procedure for synthesis of three [18F]-labeled fluoroalkyl triphenylphosphonium salts ([18F]FATPs) via two-step simple nucleophilic substitution reactions to develop new myocardial imaging agents for positron emission tomography (PET). The total reaction time of [18F]FATPs was within 60?min, and the overall decay-corrected radiochemical yield was approximately 15?30% (decay corrected). Radiochemical purity was >98% according to analytical high-performance liquid chromatography (HPLC). The specific activity of [18F]FATPs was >6.1?TBq/μmol. The [18F]FATPs exhibited higher first-pass extraction fraction values in isolated heart, higher uptake in the myocardium, and a more rapid clearance from the liver and lung than [13N]NH3 in normal rats. The images from rats with an occluded left coronary artery demonstrated sharply defined myocardial defects in the corresponding area of the myocardium. This imaging technology may enable high-throughput, multiple studies daily and wide distribution of PET myocardial studies in clinic. ? 2021, Springer Science+Business Media, LLC, part of Springer Nature.