title: Radiosynthesis and evaluation of 18F-labeled aliphatic phosphonium cations as a myocardial imaging agent for positron emission tomography.
abstract: BACKGROUND
  Lipophilic cations such as phosphonium cations penetrate the hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in the mitochondria in response to negative inner-transmembrane potentials. The present study reports the radiosynthesis and evaluation of (18)F-labeled aliphatic triphenylphosphonium cations as a potential agent for myocardial imaging by using PET.
  
  
  METHODS
  (7-[(18)F]fluoroheptyl)triphenylphosphonium salt ([(18)F]3) and (8-[(18)F]fluorooctyl)triphenylphosphonium salt ([(18)F]6) were radiolabeled by means of two-step nucleophilic substitution reactions. We measured the log P value of [(18)F]3 and [F]6 to assess the appropriate range of lipophilicity for their suitability as PET myocardial imaging agents. Normal rats were imaged with microPET after intravenous injection of 37 MBq of [(18)F]3 and [(18)F]6. To determine the pharmacokinetics, a region of interest was drawn around the heart, and time-activity curves of [(18)F]3 and [(18)F]6 were generated to obtain the counts per pixel per second.
  
  
  RESULTS
  The radiolabeled compounds [(18)F]3 and [(18)F]6 were synthesized with 18-25% yield. The radiochemical purity was greater than 98% on the basis of the analytical high-performance liquid chromatography system, and the specific activity was greater than 160-170 Ci/mmol. The log P value of the tracers was 2.52 ± 0.01 ([(18)F]3) and 2.91 ± 0.02 ([(18)F]6). Myocardium-to-liver ratios of [(18)F]3 and [(18)F]6 were 2.59 and 1.07, respectively, 10 min after injection, whereas the myocardium-to-lung ratios were 5.57 and 3.35, respectively. In addition, [(18)F]3 and [(18)F]6 showed intense, homogenous uptake in the myocardium.
  
  
  CONCLUSIONS
  (18)F-labeled aliphatic phosphonium cations [(18)F]3 and [(18)F]6 might have potential as novel myocardial agents for PET and could prove useful in clinical cardiac PET/computed tomography applications.
authors: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
authors: Dong-Yeon
authors: DY
authors: Kim
authors: Hyeon Sik
authors: HS
authors: Kim
authors: Jung-Joon
authors: JJ
authors: Min
mesh_terms: D000818:Animals; D002412:Cations / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D006321:Heart / Q000000981:diagnostic imaging*; D008297:Male; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002412:Cations; D005462:Fluorine Radioisotopes; D009943:Organophosphorus Compounds