BORONATED PORPHYRINS FOR NEUTRON CAPTURE THERAPY

10B(n，α)7Li反应在中子俘获热中的应用 (NCT)为放射治疗提供了潜在的最佳条件。 硼在肿瘤细胞中的生理定位允许选择性 在辐射场内对癌细胞的照射，如 He和Li离子在组织中的直径约为1个细胞(约10米)。 这些辐射的高度相对生物效应提供了 通常给予高LET辐射的优点。 最近的研究表明，包括卟啉在内的一些化合物， 显示与癌细胞的选择性结合的数量可能使其 用作运送硼到肿瘤的载体。选择性绑定 对肿瘤的硼化类似物的研究将允许从 正常组织，从而为成功的NCT提供了必要条件。 内源性卟啉(HPD)已经在临床上用于光疗， 红光被用来刺激肿瘤的细胞毒性反应。这个 明显的成功，至少在表面癌症方面，给了生物学上的 有证据表明，在肿瘤中有选择性的卟啉浓度足以 心理治疗。此外，我们还研究了甲藻的生物分布。 合成的卟啉(四苯基膦磺酸盐，或TPPS)在7个不同的 动物肿瘤模型。我们的数据以及其他人的数据表明 TPP在肿瘤中的大量积聚，因此如果硼化类似物 以同样的方式，肿瘤中的硼浓度将高达10倍 这是治疗所需要的。因此，现有的数据表明，渗硼 卟啉可能提供最直接的途径来实现充分的硼定位 在肿瘤里。这种卟啉类似物的使用在概念上类似于 光疗目前正在临床上使用，具有明显的优势 由激活的中子产生的更深层次的组织渗透。 临床测试的最明显的主要领域 在中子俘获疗法中的卟啉将成为治疗脑部疾病的药物 肿瘤。在这里，血脑屏障会将卟啉排除在正常范围之外。 大脑。由于治疗容量仅限于大脑，因此清除 其他正常组织中的硼化卟啉不是必需的。我们计划 合成硼化卟啉，进行生物分布研究 动物，对成功的类似物进行动力学研究并测试这些 动物体内的化合物对器官的毒性由分布指示 学习。

Utilization of the 10B(n,Alpha)7Li reaction for Neutron Capture Therpay (NCT) provides potentially optimal conditions for radiotherapy. Physiological localization of boron in tumor cells permits selective irradiation of cancer cells within the radiation field, as the range of the He and Li ions is about 1 cells diameter (approximately 10M) in tissue. The high relative biological effect from these radiations provides advantages commonly accorded to high LET radiations. Recent work indicates that a number of compounds, including porphyrins, show selective binding to cancer cells in amounts which may enable their uses as vehicles for the transport of boron to tumor. Selectivve binding of the boronated analogs to tumor would allow clearance of boron from normal tissues, thus providing the condition requisite for successful NCT. Endogenous porphyrins (HpD) are already in clinical use for phototherapy, where red light is used to stimulate a cytoxic response in tumors. The evident success, at least with superficial cancers, gives biological evidence of selective concentrations of porphyrins in tumors adequate for therapy. In addition, we have investigated the biodistribution of a synthetic porphyrin (tetraphenylporphinesulfonate, or TPPS) in 7 different animal tumor models. Our data, as well as that of others, indicates abundant accumulations of TPPS in tumor, such that if boronated analogs behave in the same way, boron concentrations in tumors would be up to 10X that needed for therapy. Thus available data indicate that boronated porphyrins may provide the most direct route to adequate boron localization in tumor. Utilization of such porphyrin analogs is similar in concept to phototherapy currently being used clinically, with the distinct advantage of deeper tissue penetration produced by the activating neutrons. The most obvious prime area for clinical testing of clinical testing of porphyrins in neutron capture therapy would be the treatment of brain tumors. Here, the blood-brain barrier would exclude porphyrins from normal brain. Since the treatment volume is limited to the brain, clearance of boronated porphyrins from other normal tissues is not required. We plan to synthesize boronated porphyrins, carry out biodistribution studies in animals, conduct kinetic studies on successful analogs and test these compounds in animals for toxicity in organs indicated by the distribution studies.