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Synthesis and evaluation ofF-labeled fluoroalkyl triphenylphosphonium salts as mitochondrial voltage sensors in PET myocardial imaging

Methods in Molecular Biology, ISSN: 1940-6029, Vol: 1265, Page: 59-72
2015
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Book Chapter Description

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 threeF-labeled fluoroalkyl triphenylphosphonium salts ([F]FATPs) via two-step simple nucleophilic substitution reactions to develop new myocardial imaging agents for positron emission tomography (PET). The total reaction time of [F]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 [F]FATPs was >6.1 TBq/ μmol. The micro-PET imaging studies in rats showed an initial spike of radioactivity, followed by myocardial retention and rapid clearance from background. 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.

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