Development of a 2-(2-Hydroxyphenyl)-1H-benzimidazole-Based Fluorescence Sensor Targeting Boronic Acids for Versatile...

Boron neutron capture therapy (BNCT) is an attractive approach to treating cancers. Currently, only one ¹⁰B-labeled boronoagent (Borofalan, BPA) has been approved for clinical BNCT in Japan, and methods for predicting and measuring BNCT efficacy must be established to support the development of next-generation ¹⁰B-boronoagents. Fluorescence sensors targeting boronic acids can achieve this because the amount and localization of ¹⁰B in tumor tissues directly determine BNCT efficacy; however, current sensors are nonoptimal given their slow reaction rate and weak fluorescence (quantum yield < 0.1). Herein, we designed and synthesized a novel small molecular-weight fluorescence sensor, BITQ, targeting boronic acids. In vitro qualitative and quantitative properties of BITQ were assessed using a fluorophotometer and a fluorescence microscope together with BPA quantification in blood samples. BITQ exhibited significant quantitative and selective fluorescence after reacting with BPA (post-to-pre-fluorescence ratio = 5.6; quantum yield = 0.53); the fluorescence plateaued within 1 min after BPA mixing, enabling the visualization of intracellular BPA distribution. Furthermore, BITQ quantified the BPA concentration in mouse blood with reliability comparable with that of current methods. This study identifies BITQ as a versatile fluorescence sensor for analyzing boronic acid agents. BITQ will contribute to ¹⁰B-boronoagent development and promote research in BNCT.