In vitro and in vivo characterization of 2-deoxy-2-18FFluoro-D- mannose as a tumor-imaging agent for PET

Shozo Furumoto, Ryo Shinbo, Ren Iwata, Yoichi Ishikawa, Kazuhiko Yanai, Takashi Yoshioka, Hiroshi Fukuda

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

2-Deoxy-2-18F-fluoro-D-mannose (18F-FDM) is an 18F-labeled mannose derivative and a stereoisomer of 18F-FDG. Our preliminary study demonstrated that 18F-FDM accumulated in tumors to the same extent as 18F-FDG, with less uptake in the brain and faster clearance from the blood. However, detailed studies on the uptake of 18F-FDM in tumors have not been conducted. We undertook this study to establish a practical method of 18F-FDM synthesis based on an 18F-nucleophilic substitution (SN2) reaction and to advance the biologic characterization of 18F-FDM for potential application as a tumor-imaging agent. Methods: We synthesized 4,6-O-benzylidene-3-O-ethoxymethyl-1-O-methyl-2-O-trifluoromethanesulfonyl- b-D-glucopyranoside as a precursor for the nucleophilic synthesis of 18F-FDM. The precursor was radiofluorinated with 18F-KF/ Kryptofix222, followed by removal of the protecting groups with an acid. 18F-FDM was purified by preparative highperformance liquid chromatography and then subjected to in vitro evaluation regarding phosphorylation by hexokinase as well as uptake and metabolism in AH109A tumor cells. The in vivo properties of 18F-FDM were examined in Donryu rats bearing AH109A tumor cells by biodistribution studies and imaging with a smallanimal PET system. Results: We radiosynthesized 18F-FDM in sufficient radiochemical yields (50%-68%) with excellent purities (97.6%-98.7%). 18F-FDM was phosphorylated rapidly by hexokinase, resulting in 98% conversion into 18F-FDG-6-phosphate within 30 min. Tumor cells showed significant uptake of 18F-FDM with time in vitro, and uptake was dose-dependently inhibited by D-glucose. 18F-FDM injected into tumor-bearing rats showed greater uptake in tumors (2.17 ± 0.32 percentage injected dose per gram [%ID/g]) than in the brain (1.42 ± 0.10 %ID/g) at 60 min after injection. PET studies also revealed the tumor uptake of 18FFDM (quasi-standardized uptake value, 2.83 ± 0.22) to be the same as that of 18F-FDG (2.40 ± 0.30), but the brain uptake of 18F-FDM (1.89 ± 0.13) was ≈30% lower than that of 18F-FDG (2.63 ± 0.26). Conclusion: We prepared 18F-FDM with good radiochemical yield and purity by an SN2 reaction. We demonstrated that 18FFDM had adequate tumor cell uptake by a metabolic trapping mechanism and can afford high-contrast tumor images with less uptake in the brain, indicating that 18F-FDM has almost the same potential as 18F-FDG for PET tumor imaging, with better advantages with regard to the imaging of brain tumors. COPYRIGHT

Original languageEnglish
Pages (from-to)1354-1361
Number of pages8
JournalJournal of Nuclear Medicine
Volume54
Issue number8
DOIs
Publication statusPublished - 2013 Aug 1

Keywords

  • Cancer
  • F-fluorodeoxy mannose
  • Hexokinase
  • PET
  • S2 reaction

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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