sup 18^F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with ^sup 18^F-FDG and ^sup 11^C-Methionine PET

Purpose The purpose of this study was to evaluate the usefulness of L-4-borono-2-18F-fluoro-phenylalanine (18F-FBPA) as a tumor-specific probe, in comparison to 18F-FDG and 11C-methionine (Met), focusing on its transport selectivity by L-type amino acid transporter 1 (LAT1), which is highly upregulated in cancers. Methods Cellular analyses of FBPA were performed to evaluate the transportablity and Km value. PET studies were performed in rat xenograft models of C6 glioma (n=12) and in rat models of turpentine oil-induced subcutaneous inflammation (n=9). The kinetic parameters and uptake values on static PET images were compared using the one-tissue compartment model (K1, k2) and maximum standardized uptake value (SUVmax). Results The cellular analyses showed that FBPA had a lower affinity to a normal cell-type transporter LAT2 and induced less efflux through LAT2 among FBPA, Met, and BPA, while the efflux through LAT1 induced by FBPA was similar among the three compounds. The Km value of 18F-FBPA for LAT1 (196.8±11.4 [mu]M) was dramatically lower than that for LAT2 (2813.8±574.5 [mu]M), suggesting the higher selectivity of 18F-FBPA for LAT1. K1 and k2 values were significantly smaller in 18F-FBPA PET (K1=0.04±0.01 ml/ccm/min and k2=0.07±0.01 /min) as compared to 11C-Met PET (0.22±0.09 and 0.52±0.10, respectively) in inflammatory lesions. Static PET analysis based on the SUVmax showed significantly higher accumulation of 18F-FDG in the tumor and inflammatory lesions (7.2±2.1 and 4.6±0.63, respectively) as compared to both 18F-FBPA (3.2±0.40 and 1.9±0.19) and 11C-Met (3.4±0.43 and 1.6±0.11). No significant difference was observed between 18F-FBPA and 11C-Met in the static PET images. Conclusion This study shows the utility of 18F-FBPA as a tumor-specific probe of LAT1 with low accumulation in the inflammatory lesions.