Biomedical applications of 10B and 11B NMR

This review focuses mainly on the detection and investigation of molecules used for boron neutron capture therapy (BNCT) by 10B and 11B NMR. In this binary radiation treatment, boron-containing molecules (also called 'BNCT agents') enriched in the 10B isotope, are targeted to the tumor, and irradiated with thermal or epithermal neutrons. Capture of these neutrons by 10B nuclei generates cell-damaging radiation, confined to single cell dimensions. NMR research efforts have primarily been applied in two directions: first, to investigate the metabolism and pharmaco-kinetics of BNCT agents in-vivo, and second, to use localized NMR spectroscopy and/or MRI for non-invasive mapping of the administered molecules in treated animals or patients. While the first goal can be pursued using 11B NMR for natural-abundance samples (80% 11B / 20% 10B), molecules used in the actual treatment are > 95% enriched in 10B, and must therefore be detected by 10B NMR. Both 10B (spin 3) and 11B (spin 3/2) are quadrupolar nuclei, and their typical relaxation times, in common BNCT agents in biological environments, are rather short. This poses some technical challenges, particularly for MRI, which will be reviewed, along with possible solutions. The first attempts at 11B NMR and MRI detection of BNCT agents in biological tissue were conducted over a decade ago. Since then, results from 11B MRI in laboratory animals and in humans have been reported, and 11B NMR spectroscopy provided interesting and unique information about the metabolism of some BNCT agents in cultured cells. 10B NMR was applied either 'indirectly' (in double-resonance experiments involving coupled protons), but also by direct 10B MRI in mice. However, no results involving the NMR detection of 10B-enriched compounds in treated patients have been reported yet.