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Trifluoroborate boronophenylalanine (BBPA) is a boron amino acid analog of 4‐boronophenylalanine (BPA) but with a trifluoroborate group (−BF3−) instead of a carboxyl group (−COOH). Clinical studies have shown that 18F−labeled BBPA ([18F]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 [18F]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 [18F]BBPA‐PET imaging in various tumor models, highlighting its broad applicability for both [18F]BBPA‐PET and BBPA‐BNCT. [18F]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 [18F]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. [ABSTRACT FROM AUTHOR]

Medullary thyroid carcinoma (MTC) can only be cured through the excision of all metastatic lesions, but current clinical practice fails to localize the disease in 29% to 60% of patients. Previously, we developed a fibroblast activation protein inhibitor (FAPI)-based covalent targeted radioligand (CTR) for improved detection sensitivity and accuracy. In this first-in-class clinical trial, we head-to-head compared [68Ga]Ga-CTR-FAPI PET-CT and [18F]fluorodeoxyglucose ([18F]FDG) PET-CT in 50 patients with MTC. The primary endpoint was the patient-based detection rate, with [68Ga]Ga-CTR-FAPI exhibiting higher detection than [18F]FDG (98% vs. 66%, P = 0.0002). This improved detection was attributed to increased tumor uptake (maximum standardized uptake value = 11.71 ± 9.16 vs. 2.55 ± 1.73, P < 0.0001). Diagnostic accuracy, validated on lesions with gold-standard pathology, was greater for [68Ga]Ga-CTR-FAPI compared with [18F]FDG (96.7% vs. 43.3%, P < 0.0001). Notably, the management of 32% of patients was altered following [68Ga]Ga-CTR-FAPI PET-CT, and the surgical plan was changed for 66.7% of patients. Overall, [68Ga]Ga-CTR-FAPI PET-CT provided superior detection and diagnostic accuracy compared with [18F]FDG PET-CT, enabling precision management of patients with MTC. Significance: In this first-in-class clinical trial of CTR, [68Ga]Ga-CTR-FAPI demonstrated an improved patient-based detection rate (98%), tumor uptake (maximum standardized uptake value = 11.71 ± 9.16), and pathology-validated diagnostic accuracy (96.7%) compared with the currently approved method in MTC treatment. It directly altered management in 32% of patients, enabling precision diagnosis and management of MTC. See related commentary by Witney, p. 264., (©2024 The Authors; Published by the American Association for Cancer Research.)