Pozzi Emiliano C C, Trivillin Verónica A, Colombo Lucas L, Monti Hughes Andrea, Thorp Silvia I, Cardoso Jorge E, Garabalino Marcela A, Molinari Ana J, Heber Elisa M, Curotto Paula, Miller Marcelo, Itoiz Maria E, Aromando Romina F, Nigg David W, Schwint Amanda E
Radiat Environ Biophys. 2013 Nov;52(4):481-91. doi: 10.1007/s00411-013-0490-9.
Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For each rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks post-irradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 ± 6.6 for Sham, 7.8 ± 4.1 for Beam only, 4.4 ± 5.6 for BPA-BNCT I and 0.45 ± 0.20 for BPA-BNCT II; tumor nodule weight was 750 ± 480 mg for Sham, 960 ± 620 mg for Beam only, 380 ± 720 mg for BPA-BNCT I and 7.3 ± 5.9 mg for BPA-BNCT II. The BPA-BNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.
硼中子俘获疗法（BNCT）被用于治疗无法治愈的结直肠癌肝转移。利用大鼠肝转移的实验模型，我们最近证明，以肿瘤处13 Gy的剂量进行硼苯丙氨酸介导的BNCT（BPA-BNCT）在3周的随访中具有治疗效果。本研究的目的是基于对个体大鼠的回顾性剂量评估，在5周随访时评估剂量反应。将BDIX大鼠接种同基因结肠癌细胞DHD/K12/TRb。荷瘤动物分为三组：BPA-BNCT组（n = 19）、仅照射组（n = 8）和假手术组（n = 7）（进行匹配操作，不进行治疗）。对每只大鼠原位测量中子通量，并在照射前的血液样本中测量硼含量，以进行回顾性个体剂量评估。为了进行统计分析（方差分析），根据吸收的肿瘤剂量将BPA-BNCT组的个体数据合并，BPA-BNCT I组：4.5 - 8.9 Gy，BPA-BNCT II组：9.2 - 16 Gy。照射后5周，假手术组治疗后与治疗前的肿瘤表面积比为12.2±6.6，仅照射组为7.8±4.1，BPA-BNCT I组为4.4±5.6，BPA-BNCT II组为0.45±0.20；肿瘤结节重量假手术组为750±480 mg，仅照射组为96±620 mg，BPA-BNCT I组为380±720 mg，BPA-BNCT II组为7.3±5.9 mg。BPA-BNCT II组表现出统计学上显著的肿瘤控制效果，且无肝脏毒性。确定肿瘤反应和显著肿瘤控制的潜在阈值剂量分别为6.1 Gy和9.2 Gy。
