A Bis‐Boron Amino Acid for Positron Emission Tomography and Boron Neutron Capture Therapy

Abstract Trifluoroborate boronophenylalanine (BBPA) is a boron amino acid analog of 4‐boronophenylalanine (BPA) but with a trifluoroborate group (−BF 3 − ) instead of a carboxyl group (−COOH). Clinical studies have shown that 18 F−labeled BBPA ([ 18 F]BBPA) can produce high‐contrast tumor images in positron emission tomography (PET). Beyond PET imaging, BBPA is a theranostic agent for boron neutron capture therapy (BNCT). Because BBPA possesses an identical chemical structure to BNCT and PET, it can potentially predict the boron concentration for BNCT using [ 18 F]BBPA‐PET. The synthesis of BBPA was achieved by selectively fluorinating the α‐aminoborate compound, taking advantage of the varying rates of solvolysis of the B−F bond. The study showcased the high‐contrast [ 18 F]BBPA‐PET imaging in various tumor models, highlighting its broad applicability for both [ 18 F]BBPA‐PET and BBPA‐BNCT. [ 18 F]BBPA‐PET tumor uptake remains consistent across various doses, including those used in BNCT. This enables accurate estimation of the boron concentration in tumors using [ 18 F]BBPA‐PET. With its dual boron structure, BBPA increases boron concentration in tumor cells and tumor tissues compared to BPA. Thus, less boron carrier is needed. This study introduces a new theranostic boron carrier that enhances boron accumulation in tumors, predicts boron concentration, and enhances the accuracy and effectiveness of BNCT.