ACTIVATION OF ANTI-CANCER AGENTS WITH ULTRASOUND

这项研究的总体目标是开发一种新的 基于活化和/或递送的癌症治疗模式 抗癌剂通过强烈的超声波曝光。 初步证据 已经表明可以“激活”抗癌剂， 以类似于光激活的方式通过超声检测血卟啉 在光动力疗法中。由于超声波可以定位到 尤其是使用相控阵技术 目前正在开发中的这项技术有许多优点 光学技术来激活药物。 此外，还有 有吸引力的可能性，声学激活，或化学 修改，广泛的药物原位以及创造 来自惰性原药的高反应性药物， 空化核 这种用于癌症治疗的药物输送方法 被称为声动力疗法（SDT）。 除了 血卟啉、另外的氧活性化合物，包括其它 卟啉，阿霉素，二氢卟酚，酞菁，细菌叶绿素， 和阳离子染料，将测定超声诱导的细胞毒性， 使用大鼠9 L胶质肉瘤和人HL 60的集落形成测定 早幼粒细胞培养系统。 本发明化合物的体内杀肿瘤活性 最有希望的试剂将使用大鼠9 L和兔VX 2进行测定 两种癌都被引入宿主动物的大腿。 肿瘤生长 将沿着确定不同对照组和处理组的 药物动力学、组织分布和肿瘤血流。 的 用注入的空化核（稳定的）增强SDT的可能性 微泡）将被探索作为假设的测试， 与声空化有关的声化学相互作用是主要的 机制来解释有希望的初步结果， 通过SDT获得。 特别令人感兴趣的是确定 组织和细胞部位的药物浓度和声化学 互动

The overall goal of this research is to develop a new therapeutic modality for cancer based on activation and/or delivery of anticancer agents by intense ultrasound exposure. Preliminary evidence has shown that it is possible to "activate" the anticancer agent hematoporphyrin by ultrasound in a manner analogous to light activation in photodynamic therapy . Since ultrasound can be localized deep into tissues with precision, particularly using the phased array technology currently under development, the technique promises numerous advantages over optical techniques for drug activation. In addition, there exists the attractive possibility of acoustically activating, or chemically modifying, a wide range of pharmaceuticals in situ as well as creating highly reactive drugs from inert protopharmaceuticals encapsulated with cavitation nuclei. This approach to drug delivery for cancer treatment has been called sonodynamic therapy (SDT). In addition to hematoporphyrin, additional oxygen active compounds including other porphyrins, adriamycin, chlorins, phthalocyanines, bacteriochlorophylls, and cationic dyes, will be assayed for ultrasound induced cytotoxicity by colony formation assays using rat 9L gliosarcoma and human HL 60 promyelocytic cell culture systems. In vivo tumoricidal activity of the most promising agents will be assayed using the rat 9L and the rabbit VX2 carcinoma both introduced into the thigh of host animals. Tumor growth of various control and treatment groups will be determined along with drug kinetics, tissue distribution, and tumor blood flow. The possibility of enhancing SDT with injected cavitation nuclei (stabilized microbubbles) will be explored as a test of the hypothesis that sonochemical interactions related to acoustic cavitation is the primary mechanism to explain the promising preliminary results which have been obtained with SDT. Of particular interest will be the determination of tissue and cellular sites of drug concentration and sonochemical interaction.