Boron delivery agents for neutron capture therapy of cancer

Abstract

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope, boron-10, is irradiated with neutrons to produce high energy alpha particles. This review will focus on tumor-targeting boron delivery agents that are an essential component of this binary system. Two low molecular weight boron-containing drugs currently are being used clinically, boronophenylalanine (BPA) and sodium borocaptate (BSH). Although they are far from being ideal, their therapeutic efficacy has been demonstrated in patients with high grade gliomas, recurrent tumors of the head and neck region, and a much smaller number with cutaneous and extra-cutaneous melanomas. Because of their limitations, great effort has been expended over the past 40 years to develop new boron delivery agents that have more favorable biodistribution and uptake for clinical use. These include boron-containing porphyrins, amino acids, polyamines, nucleosides, peptides, monoclonal antibodies, liposomes, nanoparticles of various types, boron cluster compounds and co-polymers. Currently, however, none of these have reached the stage where there is enough convincing data to warrant clinical biodistribution studies. Therefore, at present the best way to further improve the clinical efficacy of BNCT would be to optimize the dosing paradigms and delivery of BPA and BSH, either alone or in combination, with the hope that future research will identify new and better boron delivery agents for clinical use.

Boron and Health

“…44 Glioblastomların tedavisinde bor bileşiklerinin kullanılmasıyla birlikte Bor Nötron Yakalama Tedavisi [Boron Neutron Capture Therapy (BNCT)] ile bor bileşiklerinin sentezine odaklanan çalışmaların sayısı artmıştır. [45][46][47][48] Düşük molekül ağırlıklı bor içeren ilaçlar olan borfenilalanin ve sodyum borkaptat beyin tümörlerinin tedavisinde kullanılmaya başlamıştır. 46 BNCT metodu güncel olarak kanser tedavilerinde kullanılmaya başlanmıştır.…”

Boron neutron capture therapy of cancer: Critical issues and future prospects

“…The third‐generation boron‐containing agents mainly consist of a stable boron cluster attached through a hydrolytically stable linkage to a tumor‐targeting moiety, such as low or high molecular weight agents . Low molecular weight agents include boron‐containing amino acids, polyhedral boranes, biochemical precursors, DNA‐binding agents, glucose, mannose, ribose, gulose, fucose, galactose, maltose, lactose molecules, phosphates, phosphonates, phenylureas, thioureas, nitroimidazoles, amines, benzamides, isocyanates, nicotinamides, azulenes, and dequalinium derivatives.…”

“…To obtain satisfactory results with BNCT, it is crucial to identify the minimal dose required for the long‐term survival of cancer patients. To address this issue, the correlation between and radiation dose and tumor control must be identified . Furthermore, at present, the best way to improve the clinical efficacy of BNCT would be to optimize the dosing paradigms and delivery of BPA and BSH, either alone or in combination.…”

“…Furthermore, at present, the best way to improve the clinical efficacy of BNCT would be to optimize the dosing paradigms and delivery of BPA and BSH, either alone or in combination. Hopefully, future research will identify new and better boron delivery agents for clinical use . Almost all major advances in cancer therapy have come from randomized clinical trials.…”

Physical modification of carbon nanotubes with a dendrimer bearing terminal mercaptoundecahydrododecaborates (Na2B12H11S)

“…Moreover, extensive research has been published on drug delivery systems (DDSs) using PAMAM dendrimers. [1h,1i,14] Although many reports describe applications of surface‐modified SWCNTs as NIR‐II photoluminescence imaging agents and DDSs,[8] cases where the SWCNTs serve as both the bioimaging and BNCT agent have not yet been reported. Herein, we describe the synthesis of a new PAMAM dendrimer that bears terminal BSH units as a surface modifier for SWCNTs, which results in the formation of a SWCNT/B 12 ‐cluster nanohybrid.…”