18F-BPA as a surrogate tracer for BPA in BNCT: comparative analysis of transport mechanisms and biodistribution

Abstract 4-Borono-L-phenylalanine (BPA) is a key 10B carrier used in boron neutron capture therapy (BNCT), while its PET tracer analogue, 4-borono-2-18F-fluoro-L-phenylalanine (18F-BPA), enables non-invasive visualization of tumour boron uptake. Since BNCT efficacy depends on precise tumour boron accumulation, we evaluated whether 18F-BPA mirrors BPA’s transport and biodistribution. In vitro, BPA exhibited a highly consistent uptake profile with its non-radioactive fluorinated analogue, 2-19F-4-borono-L-phenylalanine (19F-BPA), across nine cancer cell lines (r = 0.9455, P < 0.001) and tri-iodothyronine (T3)-mediated LAT-1 inhibition markedly reduced the uptake of both BPA and 19F-BPA. In vivo, BPA and 18F-BPA showed predominant accumulation in the kidneys and pancreas in Sprague–Dawley rats, with substantially lower levels detected in other organs. Importantly, in tumour-bearing mice, the time-concentration curve of BPA and the time-activity curve of 18F-BPA in tumours were found to be highly consistent, and showed a corresponding relationship between BPA concentration and 18F-BPA activity in terms of accumulation in tumour, blood, and muscle (r = 0.9623, P < 0.0001). Collectively, these findings confirm that BPA and 18F-BPA not only share LAT-1-mediated transport mechanisms, but also exhibit similar pharmacokinetics and tumour-specific accumulation. This substantiates the use of 18F-BPA as a reliable surrogate for visualizing BPA biodistribution and optimizing patient-specific BNCT treatment planning.