title: Effect of methoxy group position on biological properties of18F-labeled benzyl triphenylphosphonium cations.
abstract: BACKGROUND
  18F-labeled phosphonium cations targeting mitochondrial membrane potential would be promising for positron emission tomography (PET) myocardial perfusion imaging (MPI). The purpose of this study was to examine the influence of additional methoxy group and its different positions on myocardium uptake and pharmacokinetics properties of18F-labeled benzyl triphenylphosphonium cations.
  
  
  METHODS
  In this study, three novel18F-labeled phosphonium cations, [18F]4-(fluoromethyl)benzyltris(4-methoxyphenyl) phosphonium cation (1b), [18F]4-(fluoromethyl)benzyltris(2-methoxyphenyl) phosphonium cation (2b) and [18F]4-(fluoromethyl)benzyltris(3-methoxyphenyl) phosphonium cation (3b), were efficiently prepared by a One-Pot method starting from the substitution of non-carried-added fluoride-18. Radiotracers were purified by HPLC. Physicochemical properties, in vitro cell uptake assay, in vivo mice biodistribution and rat micro-PET imaging were investigated.
  
  
  RESULTS
  Results suggested that the position of methoxy group exhibited significant effect on the biological properties of18F-labeled benzyl triphenylphosphonium cations. The addition of methoxy group on orth- or meta-position of the radiotracers accelerated the radioactivity clearance from liver. The para-radiotracer had the highest uptake in the heart and other non-targeting organs. According to the biodistribution data, 2b (ortho-) displayed the fastest liver clearance and highest heart-to-background ratios. And its rat micro-PET images at 60min post-injection revealed a good visualization of heart and favorable heart-to-background contrast. Nevertheless, 2b exhibited a lower initial liver uptake and quicker liver clearance compared with99mTc-sestamibi.
  
  
  CONCLUSIONS
  The ortho- compound (2b) displayed the most favorable biological properties as a potential MPI agent to acquire high contrast images early after injection.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, PR China.
authors.forename: Zuoquan
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China. Electronic address: ljie74@bnu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, PR China. Electronic address: zhangxzh@xmu.edu.cn.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D005260:Female; D008099:Liver / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: C513681:18F-fluorobenzyl triphenyl phosphonium; D009943:Organophosphorus Compounds
keywords: Flouride-18; Mitochondrial membrane potential; Myocardial perfusion imaging; PET; Phosphonium cation