Photodynamic Therapy-Intraperitoneal Neoplastic Diseases

光动力疗法-腹膜内肿瘤疾病

• 批准号: 7104971
• 负责人: ELI J. GLATSTEIN
• 金额: $ 151.48万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-07 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7104971
• 关键词: neoplasm /cancer photoradiation therapy; peritoneum neoplasm; photosensitizing agents

DESCRIPTION (provided by applicant) Patients with abdominal sarcomas, ovarian and gastrointestinal carcinomas have a major risk of peritoneal seeding (PS), for which results of conventional treatments are poor. We hypothesize that the combination of debulking surgery with intraperitoneal photodynamic therapy (IP PDT) will be an effective means of treating PS. IP PDT is adaptable to a wide and variable surface area, can kill multiple logs of cells and is acceptably safe to abdominal viscera. We propose to study the three major components of PDT (photosensitizer, oxygen and light), to optimize this treatment. In Project 1, we will continue our ongoing Phase II Photofrin-based clinical trial, for IP PDT in patients with recurrent PS. In addition Project 1 will investigate the efficacy and toxicity of second generation photosensitizers (SPG) in both rodent tumor systems and in large animal normal tissue models, respectively, with the aim of developing one of these compounds for future clinical trials of IP PDT. Project 2 will investigate the relationships of both tumor oxygenation and photosensitizer concentrations obtained from patient tissues to PDT response and to characteristics of tumor nodules (size, location and vascularity) by using fluorinated nitroimidazole (FN) drugs which bind and image areas of hypoxia. In Project 3, we will study both oxygen consumption and tumor vascularity during the PDT process 1 itself, by evaluating both Photofrin and other SGP in preclinical models that utilize these FN drugs in image 1: analysis studies. In Project 4, measurements of hemoglobin saturation by non-invasive techniques and quantification of light fluence will be determined directly during IP PDT. Also as part of Project 4, we will I characterize the optical properties of tissues within the peritoneum in terms of tissue scattering and absorption. Utilizing information from these investigations, we will use a SGP in a new Phase I study to optimize IP PDT as curative treatment strategy in patients with PS.

描述（由申请人提供） 患有腹部肉瘤、卵巢癌和胃肠道癌的患者 腹膜种植（PS）的主要风险，传统的结果 治疗效果很差。我们假设减瘤手术的结合 腹腔内光动力治疗（IP PDT）将是一种有效手段 治疗PS。 IP PDT 适应广泛且可变的表面积，可以 杀死多个细胞并且对腹部内脏具有可接受的安全性。我们 提出研究PDT的三大成分（光敏剂、氧 和光），以优化这种治疗。在项目1中，我们将继续我们的 正在进行的基于 Photofrin 的 II 期临床试验，针对患有以下疾病的患者进行 IP PDT 反复出现的PS。此外，项目 1 将调查功效和 第二代光敏剂（SPG）对啮齿动物肿瘤的毒性 分别在系统和大型动物正常组织模型中，目的是 开发其中一种化合物用于 IP 的未来临床试验 太平洋夏令时。项目2将研究肿瘤氧合的关系 以及从患者组织获得的光敏剂浓度进行 PDT 肿瘤结节的反应和特征（大小、位置和 血管）通过使用氟化硝基咪唑（FN）药物结合并 缺氧的图像区域。在项目 3 中，我们将研究氧气消耗 和 PDT 过程 1 本身的肿瘤血管分布，通过评估 Photofrin 和其他 SGP 在临床前模型中使用这些 FN 药物 图 1：分析研究。在项目 4 中，血红蛋白的测量 通过非侵入性技术的饱和度和光通量的量化将 在 IP PDT 期间直接确定。此外，作为项目 4 的一部分，我们将 我描述了腹膜内组织的光学特性 组织散射和吸收方面。利用这些信息 调查后，我们将在新的 I 期研究中使用 SGP 来优化 IP PDT 作为 PS 患者的治愈性治疗策略。