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)

• DOI: 10.1111/jmi.12126
• Publication Date: 2014-03-31T13:29:26Z
• Authors: S. CHANDRA; T. AHMAD; R. F. BARTH; G. W. KABALKA
• Keywords: Neutron capture; Isotopes of boron; Mass spectrometry imaging

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