A realistic appraisal of boron neutron capture therapy as a cancer treatment modality

Abstract

Boron neutron capture therapy (BNCT) is a binary therapeutic 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 and recoiling lithium-7 nuclei. In this Commentary we will focus on a number of papers that were presented at a Symposium entitled “Current Clinical Status of Boron Neutron Capture Therapy and Paths to the Future”, which was held in September 2017 at the China National Convention Center in Beijing. Results were presented by clinicians from Japan, Finland, the United States, the China mainland and Taiwan, China who have been working in the multiple disciplines that are required for carrying out clinical BNCT. The main focus was on the treatment of patients with malignant brain tumors, recurrent tumors of the head and neck region, and cutaneous melanomas. The results obtained in treating these patients were reported in detail and, although most of the patients with brain tumors and head and neck cancer were not cured, there was evidence of some clinical efficacy. Although there are a number of problems that must be addressed, further clinical studies to evaluate the efficacy of BNCT are warranted. First, despite considerable effort by numerous investigators over the past 40 years, there still are only two boron-containing drugs in clinical use, l-boronophenylalanine (BPA) and sodium borocaptate (BSH). Therefore, until new and more effective boron delivery agents are developed, efforts should be directed to improving the dosing and delivery of BPA and BSH. Second, due to a variety of reasons, nuclear reactor-based BNCT has ended except for its use in the China mainland and Taiwan. Therefore, the future of BNCT depends upon the results of the ongoing Phase II clinical trials that are being carried out in Japan and the soon to be initiated trials that will be carried out in Finland. If the results obtained from these clinical trials are sufficiently promising, then BNCT will have a clear path to the future, especially for patients with the therapeutically challenging malignancies that in the past have been treated with reactor-based BNCT.

Targeting of peptide‐binding receptors on cancer cells with peptide‐drug conjugates

“…Clinical investigation of BNCT was mainly performed on patients with recurrent head and neck cancer, high‐grade gliomas, and advanced melanomas. [ 243 ] Despite some promising results, it was not possible to establish BNCT as viable cancer treatment modality in the clinic so far owing to the lack of optimal boron delivery agents for BNCT. [ 244 ] The demanding requirements for such compounds are (a) delivery of high amounts of boron to the tumor (20‐40 μg 10 B/g tumor) to obtain a sufficient generation of destructive LET particles; (b) tumor‐selective boron uptake with tumor‐to‐normal‐cell and tumor‐to‐blood concentration ratios of >3:1 to spare the non‐neoplastic tissue; (c) low intrinsic cytotoxicity; and (d) rapid clearance from the blood, but high persistence in the tumor.…”

Princípios e aplicações da Terapia por Captura de Nêutrons por Boro – BNCT

“…Taiwan é um dos dois únicos países que continuam com estudos clínicos (fases 1 e 2) de BNCT utilizando o reator para tratamento de câncer de cabeça e pescoço recorrente em alto estadiamento. Sua experiência na BNCT é ainda bem modesta comparada com os grupos japonês e finlandês, restringindo-se ao tratamento de dez pacientes com câncer de cabeça e pescoço e um caso de glioblastoma intracranial recorrente 15,16 .…”

Properties and Applications of Metal (M) dodecahydro-closo-dodecaborates (Mn=1,2B12H12) and Their Implications for Reversible Hydrogen Storage in the Borohydrides

“…In medicine, the most notable use that has been proposed is as a boron source in boron neutron capture therapy (BNCT), a novel cancer treatment that uses a boron-containing compound to "capture" neutron radiation and selectively target cancerous cells [167]. Sodium borocaptate, a thiol derivative of the [B 12 H 12 ] 2− anion with the chemical formula Na 2 B 12 H 11 SH (often abbreviated as BSH, as shown in Figure 18), is one of only two BNCT agents that have found extensive clinical application [168].…”