Garabalino Marcela A, Monti Hughes Andrea, Molinari Ana J, Heber Elisa M, Pozzi Emiliano C C, Cardoso Jorge E, Colombo Lucas L, Nievas Susana, Nigg David W, Aromando Romina F, Itoiz Maria E, Trivillin Verónica A, Schwint Amanda E
Department of Radiobiology, National Atomic Energy Commission, Avenida General Paz 1499, B1650KNA, San Martin, Province Buenos Aires, Argentina.
Radiat Environ Biophys. 2011 Mar;50(1):199-207. doi: 10.1007/s00411-010-0345-6. Epub 2010 Dec 5.
We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of (10)B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na(2)(10)B(10)H(10)), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.
我们之前在口腔癌实验模型中证明了不同硼中子俘获疗法（BNCT）方案的治疗效果。BNCT基于肿瘤中（10）B载体的选择性积累，随后进行中子照射。在探索BNCT治疗肝转移瘤潜在治疗效果的背景下，本研究的目的是在大鼠肝转移实验模型中进行硼生物分布研究。对不同的硼化合物和给药条件进行了测定，以确定哪些给药方案在RA - 3核反应堆的体内BNCT研究中可能具有治疗作用。总共70只BDIX大鼠在肝脏接种同基因结肠癌细胞DHD/K12/TRb，以诱导包膜下肿瘤结节的形成。接种后14天，将动物用于生物分布研究。我们评估了硼化合物硼苯丙氨酸（BPA）和GB - 10（Na₂（10）B₁₀H₁₀）的总共11种给药方案，单独或在不同剂量水平下联合使用，并采用不同的给药途径。通过原子发射光谱法对肿瘤、正常组织和血液样本进行硼含量测定。就肿瘤中的绝对硼浓度和肿瘤组织对硼的优先摄取而言，六种方案被证明在BNCT研究中可能有用。肝转移模型中肿瘤和正常组织的硼浓度值表明，在RA - 3的热中子设施中，在不超过正常组织放射耐受性的情况下，在肿瘤中达到治疗性BNCT剂量是可行的。
