A COMPARATIVE-STUDY ON THE PHARMACOKINETICS AND BIODISTRIBUTION OF BORONATED PORPHYRIN (BOPP) AND SULFHYDRYL BORON HYDRIDE (BSH) IN THE RG2 RAT GLIOMA MODEL
A COMPARATIVE-STUDY ON THE PHARMACOKINETICS AND BIODISTRIBUTION OF BORONATED PORPHYRIN (BOPP) AND SULFHYDRYL BORON HYDRIDE (BSH) IN THE RG2 RAT GLIOMA MODEL
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DOI：
10.3171/jns.1995.83.1.0086
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发表时间：
1995-07-01
影响因子：
4.1
通讯作者：
SALFORD, LG
中科院分区：
文献类型：
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作者：
CEBERG, CP;BRUN, A;SALFORD, LG
硼中子俘获疗法是一种依赖于肿瘤细胞对硼的特异性摄取的癌症治疗方法。恶性胶质瘤的浸润性生长需要硼到达并积聚在肿瘤边缘外的迁移细胞中；因此，重要的是研究新的硼化合物在周围健康脑组织中的生物分布。本研究以RG2大鼠脑胶质瘤模型为研究对象，研究了硫代氢化硼(BSH)和硼化卟啉(BOPP)在大鼠体内的生物分布和药代动力学。该模型模拟了人脑胶质瘤细胞迁移到周围大脑的特征。动物被静脉注射BSH(每克体重25微克或175微克)或BOPP(每克体重12微克硼)。对于低剂量的BSH，在肿瘤与血液的比率为0.6的情况下，在注射后约9小时，肿瘤-硼的最大含量为8ppm。在较高剂量下，相应的数字在12小时后为15ppm，肿瘤与血液的比率为0.5。对于BOPP，肿瘤硼浓度在注射后24小时达到81ppm，并保持在该范围内至少72小时。24小时时肿瘤与血液的比率略高于6，但随着血液的清除，肿瘤与血液的比率继续增加。这些结果表明，这两种化合物都沿着与迁移的肿瘤细胞相同的途径扩散到正常脑组织中，即使在远处的肿瘤细胞灶中也可以通过这种方式被吸收。
Boron neutron capture therapy is a treatment modality for cancer that depends on the specific uptake of boron by the tumor cells. The infiltrative growth of malignant gliomas requires that boron reach and accumulate in migrating cells outside the margin of the tumor; thus, it is important that the biodistribution of new boron compounds is also studied in the surrounding healthy brain tissue. This study is undertaken in the present work, in which the biodistribution and pharmacokinetics of sulfhydryl boron hydride (BSH) and boronated porphyrin (BOPP) in the RG2 rat glioma model are investigated. This model mimics the characteristics of human glioma with cells migrating into the surrounding brain.The animals were infused intravenously with either BSH (25 mu g or 175 mu g of boron per gram of body weight) or BOPP (12 mu g of boron per gram body weight). For the low dose of BSH, the maximum tumor-boron content was 8 ppm at approximately 9 hours after the infusion with a tumor-to-blood ratio of 0.6. At the higher dose, the corresponding figures were 15 ppm after 12 hours with a tumor-to-blood ratio of 0.5. For BOPP, a tumor-boron concentration of 81 ppm was achieved 24 hours after the infusion and sustained in that range for at least 72 hours. The tumor-to-blood ratio at 24 hours was slightly above 6, but continued to increase as the blood was cleared. These results indicate that both compounds are spread into the normal brain tissue following the same pathways as the migrating tumor cells and in this way can be taken up even in distant tumor cell foci.