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