Boron neutron capture therapy (BNCT) of
cancer depends on the selective delivery of a sufficient number of
boron-10 ((10)B) atoms to individual tumour cells. Cell killing results from the (10)B (n, α)(7) Li neutron capture and fission reactions that occur if a sufficient number of (10)B atoms are localized in the tumour cells. Intranuclear (10)B localization enhances the efficiency of cell killing via damage to the
DNA. The net cellular content of (10)B atoms reflects both bound and free pools of
boron in individual tumour cells. The assessment of these pools, delivered by a
boron delivery agent, currently cannot be made at subcellular-scale resolution by clinically applicable techniques such as positron emission tomography and magnetic resonance imaging. In this study, a secondary ion mass spectrometry based imaging instrument, a CAMECA IMS 3f ion microscope, capable of 500 nm spatial resolution was employed. Cryogenically prepared cultured human T98G
glioblastoma cells were evaluated for
boron uptake and retention of two delivery agents. The first, L-
p-boronophenylalanine (BPA), has been used clinically for BNCT of high-grade
gliomas, recurrent tumours of the head and neck region and
melanomas. The second, a
boron analogue of an unnatural
amino acid, 1-amino-3-borono-cyclopentanecarboxylic
acid (cis-ABCPC), has been studied in rodent
glioma and
melanoma models by quantification of
boron in the nucleus and cytoplasm of individual tumour cells. The bound and free pools of
boron were assessed by exposure of cells to
boron-free nutrient medium. Both BPA and cis-ABCPC delivered almost 70% of the pool of
boron in the free or loosely bound form to the nucleus and cytoplasm of human
glioblastoma cells. This free pool of
boron could be easily mobilized out of the cell and was in some sort of equilibrium with extracellular
boron. In the case of BPA, the intracellular free pool of
boron also was affected by the presence of
phenylalanine in the nutrient medium. This suggests that it might be advantageous if patients were placed on a low
phenylalanine diet prior to the initiation of BNCT. Since BPA currently is used clinically for BNCT, our observations may have direct relevance to future clinical studies utilizing this agent and provides support for individualized treatment planning regimens rather than the use of fixed BPA infusion protocols.