Monti Hughes Andrea, Longhino Juan, Boggio Esteban, Medina Vanina A, Martinel Lamas Diego J, Garabalino Marcela A, Heber Elisa M, Pozzi Emiliano C C, Itoiz María E, Aromando Romina F, Nigg David W, Trivillin Verónica A, Schwint Amanda E
Department of Radiobiology, Constituyentes Atomic Center, National Atomic Energy Commission (CNEA), Avenida General Paz 1499, B1650KNA, San Martín, Province Buenos Aires, Argentina.
National Research Council (CONICET), Ciudad Autonoma de Buenos Aires, Argentina.
Radiat Environ Biophys. 2017 Nov;56(4):377-387. doi: 10.1007/s00411-017-0710-9. Epub 2017 Sep 4.
Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new "B2" configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in "B1" experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94-96%) than in control (16%) and BO groups (9-38%), and did not differ significantly from the "B1" results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control.
硼中子俘获疗法（BNCT）基于硼 - 10载体在肿瘤中的选择性积聚，随后进行中子照射。2001年，我们在RA - 6核反应堆的口腔癌仓鼠颊囊模型中证明了由双丙氨酰基硼烷（硼苯基丙氨酸）介导的BNCT的治疗效果。在2007年至2011年期间，RA - 6进行了升级，使得BNCT束的性能（B2配置）得到改善。我们的目的是在新的“B2”配置下，评估口腔癌仓鼠颊囊模型中双丙氨酰基硼烷 - BNCT的放射毒性和肿瘤控制情况。我们还首次在口腔癌模型中评估了组胺对作为剂量限制组织的癌前组织中的粘膜炎的放射保护作用。将癌变的颊囊暴露于：双丙氨酰基硼烷 - BNCT；双丙氨酰基硼烷 - BNCT + 组胺；仅束流（BO）；仅束流 + 组胺；对照组：癌变，未治疗。BNCT引发了严重的粘膜炎，其发生率略高于“B1”实验（分别为86% 和67%）。仅束流引发了轻度/中度粘膜炎。组胺略微降低了双丙氨酰基硼烷 - BNCT引发的严重粘膜炎的发生率（75% 对86%），并完全预防了仅束流组动物的粘膜炎。BNCT组的肿瘤总体反应（94 - 96%）显著高于对照组（16%）和仅束流组（9 - 38%），且与“B1”结果（91%）无显著差异。组胺并未损害BNCT的治疗效果。RA - 6的B1和B2配置下的BNCT放射毒性和治疗效果是一致的。即使在这个侵袭性很强的口腔癌模型中，组胺也略微减轻了癌前组织中的粘膜炎，而不影响肿瘤控制。
