Boronophenylalanine (BPA) is the dominant boron delivery agent for boron neutron capture therapy (BNCT), and [¹⁸F]FBPA has been developed to assist the treatment planning for BPA-BNCT. However, the clinical application of BNCT has been limited by its inadequate tumor specificity due to the metabolic instability. In addition, the distinctive molecular structures between [¹⁸F]FBPA and BPA can be of concern as [¹⁸F]FBPA cannot quantitate boron concentration of BPA in a real-time manner. In this study, a metabolically stable boron-derived tyrosine (denoted as fluoroboronotyrosine, FBY) was developed as a theranostic agent for both boron delivery and cancer diagnosis, leading to PET imaging-guided BNCT of cancer. [¹⁸F]FBY was synthesized in high radiochemical yield (50%) and high radiochemical purity (98%). FBY showed high similarity with natural tyrosine. As shown in in vitro assays, the uptake of FBY in murine melanoma B16-F10 cells was L-type amino acid transporter (LAT-1) dependent and reached up to 128 μg/10⁶ cells. FBY displayed high stability in PBS solution. [¹⁸F]FBY PET showed up to 6 %ID/g in B16-F10 tumor and notably low normal tissue uptake (tumor/muscle = 3.16 ± 0.48; tumor/blood = 3.13 ± 0.50; tumor/brain = 14.25 ± 1.54). Moreover, administration of [¹⁸F]FBY tracer along with a therapeutic dose of FBY showed high accumulation in B16-F10 tumor and low normal tissue uptake. Correlation between PET-image and boron biodistribution was established, indicating the possibility of estimating boron concentration via a noninvasive approach. At last, with thermal neutron irradiation, B16-F10 tumor-bearing mice injected with FBY showed significantly prolonged median survival without exhibiting obvious systemic toxicity. In conclusion, FBY holds great potential as an efficient theranostic agent for imaging-guided BNCT by offering a possible solution of measuring local boron concentration through PET imaging.

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