Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron delivery and retention at subcellular‐scale resolution in human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS)
Boron Compounds
0301 basic medicine
Microscopy, Confocal
Time Factors
Phenylalanine
Sodium
Intracellular Space
Spectrometry, Mass, Secondary Ion
Boron Neutron Capture Therapy
3. Good health
03 medical and health sciences
0302 clinical medicine
Isotopes
Cell Tracking
Cell Line, Tumor
Potassium
Humans
Calcium
Glioblastoma
Boron
DOI:
10.1111/jmi.12126
Publication Date:
2014-03-31T13:29:26Z
AUTHORS (4)
ABSTRACT
SummaryBoron neutron capture therapy (BNCT) of cancer depends on the selective delivery of a sufficient number of boron‐10 (10B) atoms to individual tumour cells. Cell killing results from the 10B (n, α)7Li neutron capture and fission reactions that occur if a sufficient number of 10B atoms are localized in the tumour cells. Intranuclear 10B localization enhances the efficiency of cell killing via damage to the DNA. The net cellular content of 10B 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.
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