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Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS

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Abstract

The ability of secondary ion mass spectrometry (SIMS) to provide high sensitivity imaging of elements and small-medium mass molecules in biological tissues and cells, makes it a very powerful tool for drug distribution studies. Here we report on the application of a high-resolution dynamic SIMS instrument for the quantification and localisation of therapeutic levels of the BNCT agent L-para-(dihydroxyboryl)-phenylalanine (BPA) in primary cell cultures from human patients exhibiting glioblastoma multiform tumours. Boron uptake and distribution was determined quantitatively as a function of cell-sampling location and different treatment regimes. Importantly, BPA was found to accumulate in cancer cells invading the ‘brain around tumour’ tissue in addition to the main tumour site. Pre-treatment of samples with L-tyrosine was found not to increase the uptake of BPA, nor change the intracellular drug distribution. In cultured cells from the tumour core and brain around tumour, with and without L-tyrosine pre-treatment, normalised boron-related signals were higher from cell nuclei than from cytoplasm. An efflux treatment was found to reduce BPA levels, but at a rate slower than the original uptake, and did not affect the intracellular drug distribution. To the best of our knowledge, these data represent the first published study of BPA uptake and L-amino acid pre-treatment in cultured primary human cells using dynamic SIMS, and the most detailed, subcellular distribution study of a BNCT agent in any cellular system.

Graphical abstract: Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS

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Publication details

The article was received on 15 Jul 2019, accepted on 30 Aug 2019 and first published on 17 Sep 2019


Article type: Paper
DOI: 10.1039/C9AN01336A
Analyst, 2019, Advance Article

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    Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS

    S. Aldossari, G. McMahon, N. P. Lockyer and K. L. Moore, Analyst, 2019, Advance Article , DOI: 10.1039/C9AN01336A

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