PHOTOTHERAPY OF INTRACAVITARY SPACES

腔内空间的光疗

• 批准号: 3853179
• 负责人: A RUSSO
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3853179
• 关键词: athymic mouse; combination cancer therapy; disease /disorder model; dogs; drug administration routes; drug delivery systems; drug screening /evaluation; heme; laboratory mouse; laser therapy; light adverse effect; luminescence; malignant ascites; mesothelioma; neoplasm /cancer immunotherapy; neoplasm /cancer photoradiation therapy; nonvisual photosensitivity; ovary neoplasms; peritoneum neoplasm; pharmacokinetics; photosensitizing agents; porphyrins; radiation therapy dosage; thorax neoplasm; tissue /cell culture

The use of hematoporphyrin derivative and other photosensitizing agents in combination with light activation is currently being investigated as an anti-tumor modality for the treatment of intraperitoneal and intrathoracic tumors. A major advantage of this modality is the apparent selective retention of the sensitizing dye within tumors. A murine ascites ovarian carcinoma and a human ovarian tumor have been used to study the characteristics of drug distribution in the peritoneal cavity. Initially, murine models were used to study the tolerance of the thoracic cavity structures to the phototherapy techniques being explored. The limitations of the murine model has required the extensions of the investigation to the canine model for evaluation of the toxicity of Phototherapy. Different wavelengths of light, different laser delivery systems, different sensitizers, different doses of energy, different modes of drug administration, and different monitoring devices were studied. We have shown that Phototherapy can be used to effectively treat a murine ascites tumor. We have also shown that in both the murine and the canine model, the peritoneal serosal surface is tolerant of at least 0.5 J/cm2 and that this work can be extended to human subjects. In the murine system, we have shown that the thoracic cavity, like the peritoneal cavity, is exquisitely sensitive to treatment with red light (630 nm). The dose rate must be controlled to minimize heat buildup (less than 150 mW fiber output from a forward projecting optical fiber is usually tolerated). We have extended a toxicity study to the canine thoracic cavity and shown that structures such as the esophagus, parietal and visceral pleura, heart can tolerate 35 J/cm2 red light. Currently, there is an ongoing Phase I trial using DHE/630nm light to treat unresectal mesothelioma. Currently, 32.5J/cm has been used in the clinical treatment of mesothelioma. We are exploring the use of photoimmunotherapy as an additional means of drug delivery. An athymic murine model transplanted with human lung cancer was used to study photoimmunotherapy. Hematoporphrin was covalently bound to the specific monoclonal antibody directed against the xenograft. The results show that tumor can be eradicated and that dermatophotoxicity is eliminated. We are exploring the use of chemiluminescence as a means of light delivery to the cavitary spaces. A new class of water soluble agents arc being used. New forms of energy delivery for activation of sensitizer are being explored.

血卟啉衍生物和其它光敏剂的用途 目前正在研究与光活化相结合， 一种用于治疗腹膜内肿瘤的抗肿瘤方式， 胸内肿瘤 这种方式的一个主要优点是 肿瘤内敏化染料的明显选择性保留。 一 小鼠腹水卵巢癌和人卵巢肿瘤已经被 用于研究药物在腹膜内的分布特征 腔 最初，鼠模型用于研究对以下的耐受性： 光疗法技术的胸腔结构 探讨了 小鼠模型的局限性要求 将研究扩展至犬模型，以评价 光疗的毒性 不同波长的光， 激光传输系统，不同的敏化剂，不同剂量的 能量、不同的给药模式和不同的监测 设备进行了研究。 我们已经证明，光疗可以用来 有效治疗小鼠腹水肿瘤。 我们还表明，在 在鼠和犬模型中，腹膜浆膜表面 耐受至少0.5 J/cm 2，并且这项工作可以扩展到 人类实验对象 在小鼠系统中，我们已经证明胸部 腹腔，像腹膜腔一样，对 用红光（630 nm）处理。 必须控制剂量率， 最大限度地减少热量积聚（从正向光纤输出小于150 mW 通常容许伸出光纤）。 我们已经扩展了一个 对犬胸腔的毒性研究表明， 如食管壁层和脏层胸膜，心脏可耐受 35 J/cm 2红光。 目前，正在进行一项I期试验， DHE/630 nm光治疗未切除间皮瘤。 目前，32.5J/cm 已用于间皮瘤的临床治疗。 我们 探索使用光免疫疗法作为药物治疗的额外手段， 交付. 人肺癌裸鼠移植瘤模型的建立 用于研究光免疫疗法。 血卟啉是共价键 结合到特异性单克隆抗体， 异种移植 结果表明，肿瘤是可以根除的， 消除了皮肤光毒性。 我们正在探索使用 化学发光作为光传递到空腔空间的手段。 使用了一类新的水溶性试剂。 新型能源 正在探索用于激活敏化剂的递送。