Quantification of ¹⁰B and ¹¹B in Biological Samples in Translational Science and Clinical Applications for Boron...

Boron neutron capture therapy (BNCT) is a targeted radiotherapy that exploits the selective accumulation of the ¹⁰B isotope within tumors, followed by irradiation with low-energy neutrons to induce high linear energy transfer particles with short path lengths, resulting in localized tumor cell destruction while sparing surrounding healthy tissue. Achieving optimal therapeutic efficacy requires precise quantification of ¹⁰B and ¹¹B in biological samples such as blood, tissue, and cells to inform treatment planning, dosimetry, and patient selection. This review provides a comprehensive assessment of analytical methods for boron (isotope) determination in BNCT, covering neutron-based techniques, mass spectrometry, nuclear imaging, and spectroscopic and magnetic approaches. Each method is discussed in terms of analytical principles, sample preparation, sensitivity, isotopic specificity, invasiveness, real-time capability, infrastructure complexity, and clinical applicability. Particular emphasis is placed on spatially resolved and in vivo techniques, as well as emerging theranostic strategies that integrate boron delivery with multimodal imaging. Despite significant technological progress, the lack of widely available, real-time, non-invasive, and ¹⁰B-specific dosimetry remains a key limitation for routine clinical implementation. In particular, while positron emission tomography-based approaches such as 4-borono-2-[¹⁸F]fluoro-L-phenylalanine provide essential information on boron biodistribution for treatment planning, they reflect tracer-level pharmacokinetics and therefore offer indirect rather than absolute quantification of therapeutic boron concentrations. This review critically assesses current methodologies in the context of clinical readiness and outlines future directions to support the translation of BNCT from bench to bedside.