(18)F-FIMP: a LAT1-specific PET probe for discrimination between tumor tissue and inflammation

Positron emission tomography (PET) imaging can assist in the early-phase diagnostic and therapeutic evaluation of tumors. Here, we report the radiosynthesis, small animal PET imaging, and biological evaluation of a L-type amino acid transporter 1 (LAT1)-specific PET probe, (18)F-FIMP. This probe demonstrates increased tumor specificity, compared to existing tumor-specific PET probes ((18)F-FET, (11)C-MET, and (18)F-FDG). Evaluation of probes by in vivo PET imaging, (18)F-FIMP showed intense accumulation in LAT1-positive tumor tissues, but not in inflamed lesions, whereas intense accumulation of (18)F-FDG was observed in both tumor tissues and in inflamed lesions. Metabolite analysis showed that (18)F-FIMP was stable in liver microsomes, and mice tissues (plasma, urine, liver, pancreas, and tumor). Investigation of the protein incorporation of (18)F-FIMP showed that it was not incorporated into protein. Furthermore, the expected mean absorbed dose of (18)F-FIMP in humans was comparable or slightly higher than that of (18)F-FDG and indicated that (18)F-FIMP may be a safe PET probe for use in humans. (18)F-FIMP may provide improved specificity for tumor diagnosis, compared to (18)F-FDG, (18)F-FET, and (11)C-MET. This probe may be suitable for PET imaging for glioblastoma and the early-phase monitoring of cancer therapy outcomes.