Histamine reduces the incidence of severe mucositis induced by boron neutron capture therapy (BNCT) in field cancerized tissue in the hamster cheek pouch oral precancer model without compromising therapeutic efficacy

A.HUGHES E.C.C.; ECC POZZI; S THORP; P CUROTTO; MEDINA VA; D MARTINEL LAMAS; E RIVERA; MA GARABALINO; FARIAS; GONZALEZ; EM HEBER; ME ITOIZ; RF AROMANDO; DW NIGG; VA TRIVILLIN; AE SCHWINT

Congreso; European Histamine Research Society, 45th Annual Meeting; 2016

BNCT is based on the capture reaction between boron-10, selectively targeted to tumor tissue, and thermal neutrons which gives rise to lethal, short-range high linear energy transfer particles that selectively damage tumor tissue. We demonstrated that the double application of BNCT mediated by the boron compounds BPA+GB-10 [D(GB-10+BPA)-BNCT], 4 weeks between applications, 10 Gy total absorbed dose, had the best therapeutic effect in the hamster cheek pouch oral precancer model but induced severe mucositis in field cancerized tissue. In a clinical scenario, the reduction of oral mucositis is an unmet medical need, limiting tumor dose and affecting patients´ quality of life. We previously demonstrated for the first time the radioprotective effect of histamine in BNCT treated animals, employing BPA, without compromising BNCT therapeutic effect. The aim of the present study was to evaluate the effect of histamine in D(GB-10+BPA)-BNCT treated animals employing 2 protocols. DMBA-cancerized hamsters were treated with: (1) BNCT without Histamine; (2) BNCT+Histamine LOW concentration (1 mg/kg/day) - LONG administration (16 days); (3) BNCT+Histamine HIGH concentration (5 mg/kg/day)-SHORT administration (5 days). We evaluated histamine toxicity, % of animals with severe mucositis, % of animals with new tumors after BNCT, during 3 months after the first irradiation at RA3 nuclear reactor. Local irritation was seen at the site of histamine injection. Protocols 2 and 3 had a tendency to reduce severe mucositis versus group 1 (Respectively: 29%; 20%; 33%), without compromising therapeutic effect. Protocol 3 showed a tendency to have a greater protector effect than protocol 2. Histamine HIGH concentration-SHORT administration could be more effective to reduce the incidence of severe mucositis in field cancerized tissue treated with D(GB-10+BPA)-BNCT. Furthermore, this protocol involves fewer applications, reducing animal handling and the local irritation caused by the injection.