title: Synthesis and evaluation of [(18)F]-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.
authors.affiliation: Chinese Medicine Immunology Laboratory & Science and Technology Department, Henan University of Chinese Medicine, Jinshui East Road Boxue Road, Zhengzhou, 450046, China; Department of Nuclear Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China. Electronic address: huahuizeng@gmail.com.
authors.forename: Huahui
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Chinese Medicine Immunology Laboratory & Science and Technology Department, Henan University of Chinese Medicine, Jinshui East Road Boxue Road, Zhengzhou, 450046, China. Electronic address: wuxx-415@126.com.
authors.forename: Xiangxiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Nuclear Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.
authors.forename: Fahuan
authors.initials: F
authors.lastname: Song
authors.affiliation: Department of Nuclear Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Nuclear Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310009, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Chinese Medicine Immunology Laboratory & Science and Technology Department, Henan University of Chinese Medicine, Jinshui East Road Boxue Road, Zhengzhou, 450046, China. Electronic address: wendiliu@163.com.
authors.forename: Wendi
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D004355:Drug Stability; D005260:Female; D008564:Membrane Potentials; D008929:Mitochondria, Heart / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D011854:Radiochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D009943:Organophosphorus Compounds; D011849:Radioactive Tracers
keywords: Fluorine-18 ((18)F); Membrane potential; Myocardial imaging; Positron emission tomography (PET); Triphenylphosphonium cation