title: Synthesis of [18F]-labeled (6-fluorohexyl)triphenylphosphonium cation as a potential agent for myocardial imaging using positron emission tomography.
abstract: Lipophilic cations such as phosphonium salts penetrate the hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in mitochondria in response to the negative inner-transmembrane potentials. Thus, as newly developed noninvasive imaging agents, [(18)F]-labeled phosphonium salts may serve as molecular "voltage sensor" probes to investigate the role of mitochondria, particularly in myocardial disease. The present study reports the radiosynthesis of (6-fluorohexyl)triphenylphosphonium salt (3) as a potential agent for myocardial imaging by using positron emission tomography (PET). The reference compound of (6-[(18)F]fluorohexyl)triphenylphosphonium salt ([(18)F]3) was synthesized with 74% yield via three-step nucleophilic substitution reactions. The reference compound was radiolabeled via two-step nucleophilic substitution reactions of no-carrier-added [(18)F]fluoride with the precursor hexane-1,6-diyl bis(4-methylbenzenesulfonate) in the presence of Kryptofix 2.2.2 and K(2)CO(3). The radiolabeled compound was synthesized with 15-20% yield. The radiochemical purity was >98% by analytical HPLC, and the specific activity was >6.10-6.47 TBq/μmol. The cellular uptake assay showed preferential uptake of [(18)F]3 in cardiomyocytes. The results of biodistribution and micro-PET imaging studies of [(18)F]3 in mice and rats showed preferential accumulation in the myocardium. The results suggest that this compound would be a promising candidate for myocardial imaging.
authors.affiliation: Department of Chemistry, Dongguk University-seoul, Seoul, Korea.
authors.forename: Dong-Yeon
authors.initials: DY
authors.lastname: Kim
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Kook-Hyun
authors.initials: KH
authors.lastname: Yu
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Min
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes; D006321:Heart / Q000033:anatomy & histology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D010720:Phosphines; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D021241:Spectrometry, Mass, Electrospray Ionization; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: C573828:(6-fluorohexyl)triphenylphosphonium; D005462:Fluorine Radioisotopes; D010720:Phosphines; D019275:Radiopharmaceuticals