Boron neutron capture therapy (BNCT) is a promising cancer treatment strategy that utilizes boron-containing ligands. In this report, a series of substituted boramino acids were synthesized and evaluated, aiming to obtain metabolically stable boron-derived agents that could integrate positron emission tomography (PET) with BNCT (a theranostic agent). Based on the phenylalanine (Phe) core structure, the impact of substitution groups on tumor accumulation was studied. The agents were labeled with fluorine-18 in 27.2-66.8% yield via the 18F-19F isotope exchange reaction. In B16-F10 tumor-bearing mice, [18F]-(R)-(1-ammonio-2-(4-methoxyphenyl) ethyl) trifluoroborate (R-[18F]-5a) demonstrated the best tumor uptake (5.54 ± 2.32% ID/g based on ex vivo biodistribution and 3.5 ± 0.04% ID/g based on PET imaging with the tumor-to-muscle ratio up to 2.6) and stability compared with other tested agents. Together, R-[18F]-5a is a promising agent that could potentially integrate PET and BNCT, whose treatment efficacy is worth further evaluation in the future.
Keywords: 18F; Boramino acid; positron emission tomography (PET); tumor diagnosis.