Evaluation of Oligo-Fucoidan as a potentially beneficial adjunct to BNCT in a novel oral cancer and precancer experimental model.

Abstract

The high mortality and morbidity of Head and Neck cancer patients and the toxicity associated to oncological treatments suggest the need for more selective and non-toxic therapies. BNCT (Boron Neutron Capture Therapy) is based on the capture reaction between boron-10, selectively targeted to tumor tissue, and a thermal neutron. In this study, an oral cancer and precancer model was used to study the therapeutic effect and radiotoxicity of BNCT mediated by BPA (boronphenylalanine) [BPA-BNCT] at short and medium-term follow-up. Oligo-Fucoidan, an extract of Laminaria japonica brown seaweed, was evaluated as a potentially beneficial adjunct to BPA-BNCT. Hamsters were chemically cancerized over 8 weeks. Tumor bearing hamsters were assigned to: (CONTROL) cancerized, sham-irradiated group; BPA-BNCT 3 Gy absorbed dose to precancerous tissue; BPA-BNCT 3 Gy + Oligo-Fucoidan (200 mg/kg/day, for 16 days). Neutron irradiation was performed at the RA-3 Nuclear Reactor 3 h post administration of BPA (15.5 mg ¹⁰B/kg). Boron biodistribution and microdistribution studies were performed in BPA and BPA + Oligo-Fucoidan groups. Oligo-Fucoidan did not reduce either the incidence of moderate/severe mucositis or reduced the percentage of animals with new tumors in precancerous tissue. Oligo-Fucoidan did enhance BPA-BNCT-induced tumor response at one month (67-94%) and three months after BNCT (42-81%). To understand this effect, boron biodistribution and microdistribution studies were performed. They demonstrated a slight tendency of Oligo-Fucoidan to increase boron concentration in tumors. Oligo-Fucoidan, used in humans and clinical veterinary patients, would be a potentially beneficial adjunct to BNCT.