‘Close-to-ideal’ Tumor Boron Targeting for Boron Neutron Capture Therapy is Possible With ‘less-than-ideal’ Boron Carriers Approved for Use in Humans

Abstract

Keywords: boron compounds approved for use in humans • boron neutron capture therapy (BNCT) • BPA • GB-10 • optimization of boron tumor targeting

First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness

“…The considered BSH concentrations were equivalent to 40 ppm (parts per million) and 80 ppm of 11 B. These were chosen based on values from the literature on the 10 B-enriched BSH analogue used in BNCT in order to achieve the optimal intracellular 10 B concentration 35,46,47 . In particular, similar boron-equivalent concentration ranges of another BNCT compound, BPA, had been previously used with the same cell line in vitro 48 .…”

“…The rationale underlying BNCT consists in cancer irradiation by thermal neutrons, which results in a highly localized and mostly lethal targeting of cancer cells because of the very short range and, hence, of the high LET of the low-energy alpha particles generated in the reaction with the 10 B atoms. However, despite numerous, carefully designed and generally promising clinical trials 53,54 , BNCT struggles to establish itself in clinical routine, both because of the intrinsically challenging quest for ideal carriers to deliver radiobiologically effective concentrations of boron to cancer cells, and because of the limited availability of thermal neutron sources 35,47 . On the other hand, albeit already being a clinical reality, external beam 12 C-ion hadrontherapy, which is capable of delivering very biologically effective radiation doses with extremely high precision to the tumor target, is hampered by economic and radiobiological issues as discussed in the Introduction section.…”

“…Although measurements of 11 B incorporation by cells were not performed, both drug pre-treatment times and concentrations were chosen according to available literature data for the use of the boron-carrier BSH in BNCT, according to which the optimal conditions to reach an ideal boron concentration in cells is 20 µg per grams of tissue or 10 9 atoms per cell 58 . Indeed, although 10 B-enriched BSH is known for its poor permeabilization through cell membranes, its use is facilitated by a higher boron content compared to the other widely used boron-delivering compound, such as BPA.…”

Current data regarding the structure-toxicity relationship of boron-containing compounds

“…Findings concerning a selective 'phylogenetic' or 'cellular' toxicity of BCCs have suggested their usefulness for treating infectious diseases or some types of cancer (Park, 2004;Di Fiore, 2010;Scorei, 2011c;Scorei, 2013b;Nielsen, 2014;Schwint, 2015). In this sense, some BCCs have notable antimicrobial activity on some pathogenic species, and some molecular targets have been identified on these microorganisms (proteasomes, penicillin binding proteins, carbonic anhydrases, synthetases, etc.).…”

“…It has been suggested that BCCs exert greater toxicological effects on neoplastic than healthy cells, mainly due to their use in metabolism (Beardsley, 2003;Calabrese, 2012;Roda, 2014Schwint, 2015. In fact, BCCs have shown effects on breast, colorectal and prostate cancer (Park, 2004;Di Fiore, 2010;Scorei, 2011c;Scorei, 2013b).…”