BORONATED PORPHYRINS FOR NEUTRON CAPTURE THERAPY

~（10）B（n，α）~ 7 Li反应在中子俘获热疗中的应用 (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地 辐射场内的癌细胞的照射，作为辐射场的范围， He和Li离子在组织中约为1个细胞直径（约10 M）。 这些辐射的高相对生物效应提供了 通常符合高LET辐射的优点。 最近的研究表明，许多化合物，包括卟啉， 显示出选择性结合癌细胞的量， 用作将硼转运至肿瘤的载体。 选择性结合 的硼类似物的肿瘤将允许清除硼从 正常组织，从而提供成功NCT所必需的条件。 内源性卟啉（HpD）已经在临床上用于光疗， 其中红光用于刺激肿瘤中的细胞毒性反应。 的 明显的成功，至少在浅表性癌症中， 证明肿瘤中卟啉的选择性浓度足以 疗法 此外，我们还研究了一种 合成卟啉（四苯基卟啉磺酸盐，或TPPS）在7个不同 动物肿瘤模型。 我们的数据，以及其他人的数据，表明 TPPS在肿瘤中的大量积累，使得如果硼化类似物 以同样的方式表现，肿瘤中的硼浓度将高达10倍 治疗所需的东西 因此，现有数据表明， 卟啉可以提供最直接的途径，以充分硼定位 在肿瘤中。 这种卟啉类似物的利用在概念上类似于 目前临床上使用的光疗具有明显的优点， 由激活中子产生的更深的组织穿透。 临床试验最明显的主要领域是 卟啉在中子俘获疗法中的应用 肿瘤的 在这里，血脑屏障将卟啉从正常的 个脑袋 由于治疗体积仅限于大脑， 不需要来自其他正常组织的硼化卟啉。 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 化合物在动物中的分布所指示的器官毒性 问题研究

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.