In Vitro Exposure of Human T98G Glioblastoma Cells to Mixed BNCT Drugs

Abstract

The selective targeting with sufficient quantities of ¹⁰B atoms to the tumor cells is critical for Boron Neutron Capture Therapy (BNCT) of cancer. At present there are two BNCT drugs, p-boronophenylalanine (BPA) and sodium borocaptate (BSH), approved for use in clinical trials. Since both BPA and BSH may deliver boron to tumor cells by different mechanisms, the concept of mixing the two compounds may have the merit of providing a unique approach for attaining a higher net accumulation of boron atoms in tumor cells than would otherwise be attained by an individual compound. Clinical applications of this mixed-drug approach would require that both drugs provide ¹⁰B atoms. For laboratory research purposes, however, one can use a mixture such as ¹⁰B labeled ¹⁰BPA and ¹¹B labeled ¹¹BSH and an isotopic imaging technique of ion microscopy for studying intracellular accumulations of both ¹⁰B and ¹¹B in the same cell. Ion microscopy, based on secondary ion mass spectrometry (SIMS),1,2 is capable of quantitatively imaging the subcellular distribution of both ¹⁰B and ¹¹B atoms delivered by two different BNCT agents in the same cell since the technique distinguishes isotopes based on their mass-to-charge (m/z) ratio. The exposure of cells to two BNCT compounds mixed together may result in the enhancement of boron uptake by tumor cells. In the present study, by using ¹⁰B labeled p-boronophenylalanine-fructose (¹⁰BPA-F) and ¹¹B labeled sodium borocaptate (¹¹BSH) as a mixed-drug model we were able to image the subcellular distribution of both ¹⁰B and ¹¹B atoms independently in the same cell with ion microscopy. Such independent imaging of boron atoms from two mixed-drugs in the same cell introduces a novel approach for checking the boron delivery characteristic of two BNCT compounds combined together.