Frydryk Benitez Debora N, Palmieri Mónica A, Langle Yanina V, Monti Hughes Andrea, Pozzi Emiliano C C, Thorp Silvia I, Garabalino Marcela A, Curotto Paula, Ramos Paula S, Paparella María L, Polti Lucas, Eiján Ana, Schwint Amanda E, Trivillin Verónica A
Comisión Nacional de Energía Atómica (CNEA), Av. General Paz 1499, San Martin, Buenos Aires C1650KNA, Argentina.
Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Av. Int. Güiraldes 2160, 4 Piso, Pab. II, Ciudad Autónoma de Buenos Aires C1428EGA, Argentina.
Life (Basel). 2023 Jul 11;13(7):1538. doi: 10.3390/life13071538.
Boron neutron capture therapy (BNCT) is based on the preferential uptake of B compounds by tumors, followed by neutron irradiation. The aim of this study was to assess, in an ectopic colon cancer model, the therapeutic efficacy, radiotoxicity, abscopal effect and systemic immune response associated with (BPA/Borophenylalanine+GB-10/Decahydrodecaborate)-BNCT (Comb-BNCT) alone or in combination with Oligo-Fucoidan (O-Fuco) or Glutamine (GLN), compared to the "standard" BPA-BNCT protocol usually employed in clinical trials. All treatments were carried out at the RA-3 nuclear reactor. Boron biodistribution studies showed therapeutic values above 20 ppm B in tumors. At 7 weeks post-treatment, the ratio of tumor volume post-/pre-BNCT was significantly smaller for all BNCT groups vs. SHAM ( < 0.05). The parameter "incidence of tumors that underwent a reduction to ≤50% of initial tumor volume" exhibited values of 62% for Comb-BNCT alone, 82% for Comb-BNCT+GLN, 73% for Comb-BNCT+O-Fuco and only 30% for BPA-BNCT. For BPA-BNCT, the incidence of severe dermatitis was 100%, whereas it was significantly below 70% ( ≤ 0.05) for Comb-BNCT, Comb-BNCT+O-Fuco and Comb-BNCT+GLN. Considering tumors outside the treatment area, 77% of Comb-BNCT animals had a tumor volume lower than 50 mm vs. 30% for SHAM ( ≤ 0.005), suggesting an abscopal effect of Comb-BNCT. Inhibition of metastatic spread to lymph nodes was observed in all Comb-BNCT groups. Considering systemic aspects, CD8 was elevated for Comb-BNCT+GLN vs. SHAM ( ≤ 0.01), and NK was elevated for Comb-BNCT vs. SHAM ( ≤ 0.05). Comb-BNCT improved therapeutic efficacy and reduced radiotoxicity compared to BPA-BNCT and induced an immune response and an abscopal effect.
硼中子俘获疗法（BNCT）基于肿瘤对硼化合物的优先摄取，随后进行中子照射。本研究的目的是在异位结肠癌模型中，评估与单独使用（双对氨基苯甲酰基硼烷/硼苯丙氨酸+GB-10/十氢十硼酸）-BNCT（联合BNCT）或与低聚岩藻糖胶（O-Fuco）或谷氨酰胺（GLN）联合使用相关的治疗效果、放射毒性、远隔效应和全身免疫反应，并与临床试验中通常采用的“标准”双对氨基苯甲酰基硼烷-BNCT方案进行比较。所有治疗均在RA-3核反应堆进行。硼生物分布研究表明肿瘤中硼的治疗值高于20 ppm。治疗后7周，所有BNCT组的肿瘤体积治疗后/治疗前比值与假手术组相比均显著更小（<0.05）。“肿瘤体积缩小至初始肿瘤体积≤50%的发生率”这一参数，单独使用联合BNCT时为62%，联合BNCT+GLN时为82%，联合BNCT+O-Fuco时为73%，而双对氨基苯甲酰基硼烷-BNCT仅为30%。对于双对氨基苯甲酰基硼烷-BNCT，严重皮炎的发生率为100%，而联合BNCT、联合BNCT+O-Fuco和联合BNCT+GLN的发生率显著低于70%（≤0.05）。考虑治疗区域外的肿瘤，联合BNCT组77%的动物肿瘤体积小于50 mm，而假手术组为30%（≤0.005），表明联合BNCT具有远隔效应。在所有联合BNCT组中均观察到对淋巴结转移扩散的抑制。从全身方面考虑，联合BNCT+GLN组的CD8水平相对于假手术组升高（≤0.01），联合BNCT组的NK水平相对于假手术组升高（≤0.05）。与双对氨基苯甲酰基硼烷-BNCT相比，联合BNCT提高了治疗效果，降低了放射毒性，并诱导了免疫反应和远隔效应。
