Radiosynthesis and preliminary biological evaluation of a new 18F-labeled triethylene glycol derivative of triphenylphosphonium

Takahiro Tominaga, Hiroaki Ito, Yoichi Ishikawa, Ren Iwata, Kiichi Ishiwata, Shozo Furumoto

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Delocalized lipophilic cations such as [18F]fluorobenzyltriphenylphosphonium ([18F]FBnTP) can accumulate in mitochondria and have been used in myocardial perfusion imaging (MPI). In this study, we established a simplified method for [18F]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 18F-labeled PEGylated BnTP derivative ([18F]FPEGBnTP). In vitro cellular uptake study demonstrated that [18F]FPEGBnTP accumulated in cells in proportion to the relative intensity of mitochondrial membrane potential. Biodistribution study revealed that the heart: Liver uptake ratio of [18F]FPEGBnTP (4.00 at 60 min) was superior to that of [18F]FBnTP (1.50 at 60 min). However, [18F]FPEGBnTP showed slow blood clearance and high radioactivity uptake in bone at 120-min post-injection. These results imply the possibility of [18F]FPEGBnTP being used as a MPI agent. However, there is a need of further structural optimization and flow-dependent uptake study. A 18F-PEGylated derivative of benzyltriphenylphosphonium ([18F]FPEGBnTP) was synthesized through the reaction of the 18F-PEGylated benzyl alcohol intermediate with triphenylphosphine hydrobromide. [18F]FPEGBnTP showed higher accumulation in the heart than the organs near the heart.

Original languageEnglish
Pages (from-to)117-123
Number of pages7
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume59
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1

Keywords

  • DLCs
  • FBnTP
  • PET
  • mitochondria
  • positron emission tomography

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

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