Development of a 2-(2-Hydroxyphenyl)-1H-benzimidazole-Based Fluorescence Sensor Targeting Boronic Acids for Versatile Application in Boron Neutron Capture Therapy

SIMPLE SUMMARY: In boron neutron capture therapy (BNCT), the amount and localization of boron-10 atoms in tumor tissues directly determine the therapeutic effect. This study developed a novel fluorescence sensor, BITQ, to analyze boronic acid agents used for BNCT. Mixing BITQ and a representative (10)B-labeled boronoagent, BPA, immediately produced significant fluorescence in a highly quantitative and selective manner. BITQ enabled the visualization of BPA distribution within a living cell and quantified the concentration of BPA in mouse blood to a degree comparable with that of current methods. This study highlights the highly effective properties of BITQ as a versatile fluorescence sensor for analyzing boronic acid agents. ABSTRACT: Boron neutron capture therapy (BNCT) is an attractive approach to treating cancers. Currently, only one (10)B-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 (10)B-boronoagents. Fluorescence sensors targeting boronic acids can achieve this because the amount and localization of (10)B 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 (10)B-boronoagent development and promote research in BNCT.