title: Radiosynthesis and preliminary biological evaluation of a new (18)F-labeled triethylene glycol derivative of triphenylphosphonium.
abstract: Delocalized lipophilic cations such as [(18)F]fluorobenzyltriphenylphosphonium ([(18)F]FBnTP) can accumulate in mitochondria and have been used in myocardial perfusion imaging (MPI). In this study, we established a simplified method for [(18)F]FBnTP synthesis using triphenylphosphine hydrobromide (PPh3 •HBr) without preparing an intermediate that contains benzyl bromide structure. Applying this new method, we synthesized and evaluated a novel (18)F-labeled PEGylated BnTP derivative ([(18)F]FPEGBnTP). In vitro cellular uptake study demonstrated that [(18)F]FPEGBnTP accumulated in cells in proportion to the relative intensity of mitochondrial membrane potential. Biodistribution study revealed that the heart : liver uptake ratio of [(18)F]FPEGBnTP (4.00 at 60 min) was superior to that of [(18)F]FBnTP (1.50 at 60 min). However, [(18)F]FPEGBnTP showed slow blood clearance and high radioactivity uptake in bone at 120-min post-injection. These results imply the possibility of [(18)F]FPEGBnTP being used as a MPI agent. However, there is a need of further structural optimization and flow-dependent uptake study.
authors: Cyclotron and Radioisotope Center (CYRIC), Tohoku University, Sendai, 980-8578, Japan.|Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan.
authors: Takahiro
authors: T
authors: Tominaga
authors: Cyclotron and Radioisotope Center (CYRIC), Tohoku University, Sendai, 980-8578, Japan.|Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan.
authors: Hiroaki
authors: H
authors: Ito
authors: Cyclotron and Radioisotope Center (CYRIC), Tohoku University, Sendai, 980-8578, Japan.
authors: Yoichi
authors: Y
authors: Ishikawa
authors: Cyclotron and Radioisotope Center (CYRIC), Tohoku University, Sendai, 980-8578, Japan.
authors: Ren
authors: R
authors: Iwata
authors: Institute of Cyclotron and Drug Discovery Research, Southern Tohoku Research Institute for Neuroscience, Koriyama 963-8563, Japan.|Department of Biofunctional Imaging, Fukushima Medical University, Fukushima 960-1295, Japan.
authors: Kiichi
authors: K
authors: Ishiwata
authors: Cyclotron and Radioisotope Center (CYRIC), Tohoku University, Sendai, 980-8578, Japan.|Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan.
authors: Shozo
authors: S
authors: Furumoto
mesh_terms: D005462:Fluorine Radioisotopes / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C513681:18F-fluorobenzyl triphenyl phosphonium; D005462:Fluorine Radioisotopes; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; C028914:triethylene glycol; D011092:Polyethylene Glycols
keywords: DLCs; FBnTP; PET; mitochondria; positron emission tomography