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