Subcellular distribution of various boron compounds and implications for their efficacy in boron neutron capture therapy by Monte Carlo simulations.
Neutron capture therapy has a promising role in cancer treatment since it can achieve selectivity at the cellular level. The effect of this therapy depends on the subcellular localization of boron atoms in the target cell. Five boron compounds were investigated in this study: the monomeric and dimeric sulfhydryl boranes (BSH and BSSB), a boronated phenylalanine (BPA), and two porphyrin complexes (BOPP and VCDP). The study shows that when exponentially growing rat 9L gliosarcoma cells are exposed to an isoeffective concentration of each of the five compounds for 1 h, BOPP produces a much higher intracellular level of boron than the other four compounds; BSSB produces the second highest level, while exposure to BSH, VCDP, and BPA resulted in lower intracellular boron levels. Subcellular fractionation studies showed that most of the boron localized in the cytoplasm of the cells with all five compounds. A significantly higher boron concentration was found in the lysosomes of the cells, but the nuclei contained only minimal concentrations of boron. Computer simulations of neutron capture reactions with boron using a Monte Carlo simulation code indicated that BOPP would yield the highest potential effectiveness, followed by BSSB, BSH, VCDP, and BPA, in that order.
Nguyen
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T
Nuclear Engineering Department, Massachusetts Institute of Technology, Cambridge 02139.
Brownell
G L
GL
Holden
S A
SA
Kahl
S
S
Miura
M
M
Teicher
B A
BA
D000818:Animals; D001896:Boron Compounds / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy; D003198:Computer Simulation; D005910:Glioma / Q000378:metabolism*; D009010:Monte Carlo Method; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism*
D001896:Boron Compounds