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

Abstract

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. Cellular analyses of FBPA were performed to evaluate the transportablity and K_m 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). 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 K_m value of ¹⁸F-FBPA for LAT1 (196.8 ± 11.4 μM) was dramatically lower than that for LAT2 (2813.8 ± 574.5 μM), 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. This study shows the utility of ¹⁸F-FBPA as a tumor-specific probe of LAT1 with low accumulation in the inflammatory lesions.