Trivillin Verónica A, Pozzi Emiliano C C, Colombo Lucas L, Thorp Silvia I, Garabalino Marcela A, Monti Hughes Andrea, González Sara J, Farías Rubén O, Curotto Paula, Santa Cruz Gustavo A, Carando Daniel G, Schwint Amanda E
Department of Radiobiology, Comisión Nacional de Energía Atómica (CNEA), Avenida General Paz 1499, B1650KNA San Martin, Provincia Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
Radiat Environ Biophys. 2017 Nov;56(4):365-375. doi: 10.1007/s00411-017-0704-7. Epub 2017 Aug 8.
The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 10 DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 × 10 DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm. In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm. The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect.
本研究的目的是首次评估硼中子俘获疗法(BNCT)的远隔效应。将26只BDIX大鼠的右后腹侧皮下接种1×10个DHD/K12/TRb同基因结肠癌细胞。接种后三周,对12只带有肿瘤结节的大鼠的右腿在位于阿根廷布宜诺斯艾利斯的RA - 3核反应堆中进行BPA - BNCT(硼苯丙氨酸 - 硼)治疗,作为剂量限制组织的皮肤吸收剂量为7.5 Gy。其余14只荷瘤大鼠不进行治疗,用作对照。BNCT治疗后两周,在26只BDIX大鼠的每只大鼠的对侧左后腹侧皮下注射1×10个DHD/K12/TRb细胞。每周测量双腿的肿瘤体积,持续7周,以确定右腿对BNCT的反应,并评估右腿的BNCT对左腿肿瘤发展的潜在影响。在BNCT组中,与未产生反应的动物(治疗后/治疗前肿瘤体积≥1)相比,右腿肿瘤对BNCT产生反应的动物(治疗后/治疗前肿瘤体积<1)的对侧左肿瘤体积出现了统计学上的显著减小,即13±15 vs 271±128 mm³。此外,与未治疗的动物相比,对BNCT有反应的动物(治疗后/治疗前<1)的对侧左腿肿瘤体积出现了统计学上的显著减小,即13±15 vs 254±251 mm³。在一个简单动物模型中进行的本研究提供了原理证明,即肿瘤对BNCT的阳性反应能够诱导远隔效应。