Boron neutron capture therapy: Development of novel boron reagents and BNCT-induced immune activation

Abstract

Boron Neutron Capture Therapy (BNCT) is a type of radiation therapy that uses neutron beam. Neutron Irradiation of boron-10 results in the splitting of boron-11 to helium and lithium. The helium nucleus is alpha-ray that causes DNA double-strand breaks inducing apoptosis of cancer cells. Since the development of accelerator-based neutron generators, this therapy has been used in multiple hospitals in Japan, China, Finland and others. Recently, novel boron reagents, BTS and dipeptides with increased tumor accumulation efficacy, have been developed. Compared with currently used BPA, these reagents are highly soluble and can achieve 3-4 fold higher accumulation of boron-10 in the tumor. This significantly increases BNCT efficacy resulting in the eradication of tumor in a mouse model. In addition, mice after the BNCT treatment resist further transplantation of the tumor, suggesting the activation of vaccine-like effect. In addition, abscopal effect is observed by the administration of the new boron reagents followed by neutron exposure. This review focuses on these recent developments that suggest that BNCT induces immune responses.