Boron neutron capture therapy for the treatment of glioblastomas and extracranial tumours: As effective, more effective or less effective than photon irradiation?

Abstract

Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when nonradioactive boron-10 is irradiated with neutrons of the appropriate energy to yield high energy alpha particles (He) and recoiling lithium-7 (Li) nuclei. Since these particles have pathlengths of approximately one cell diameter, their lethality is primarily limited to boron containing cells. BNCT, therefore, can be regarded as both a biologically and a physically targeted type of radiation therapy [1]. The success of BNCT is dependent upon the selective delivery of sufficient amounts of B to cancer cells with only small amounts localized in the surrounding normal tissues. A wide variety of boron delivery agents have been synthesized [2], but only two of these currently are being used in clinical trials [1]. The first, which has been used primarily in Japan [3,4], is sodium borocaptate or BSH, and the second is a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or BPA. The latter has been used in clinical trials in the United States, Europe, and more recently in Japan [1]. Following administration of either BPA or BSH by intravenous infusion, the tumour site is irradiated with neutrons, the source of which is a nuclear reactor. Up until 1994, low-energy (En < 0.5 eV) thermal neutron beams were used primarily in Japan [3,4], but since they have a limited depth of penetration in tissues, higher energy (<10 keV) epithermal neutron beams, which have a greater depth of penetration, have been used in clinical trials in the United States [5,6], Europe [7] and now Japan [8]. In theory, BNCT is a highly selective type of radiation therapy that can target the tumour without causing excessive radiation damage to the normal tissues. Doses up to 60–70 Gy (weighted) can be delivered to B containing tumour cells within approximately one hour instead of 6–7 weeks for conventional external beam photon irradiation. However, the effectiveness of BNCT is dependent upon a relatively homogeneous distribution of B within the tumour, and this is still one of the key stumbling blocks that has limited its success. BNCT could be useful for the treatment of malignancies such as high grade gliomas, selected patients with melanoma and therapeutically refractory, recurrent tumours of the head and neck. A series of