Optical Dosimetry for Clinical Trials of Pc 4 Photodynamic Therapy

用于 Pc 4 光动力疗法临床试验的光学剂量测定

• 批准号: 7629147
• 负责人: THOMAS Harrison FOSTER
• 金额: $ 24.2万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7629147
• 关键词: Address; Apoptosis; Appearance; Area; Basal cell carcinoma; Biological; Caliber; Cells; Characteristics; Clinical; Clinical Treatment; Clinical Trials; Cutaneous; Data; Deposition; Dermatology; Disease; Dose; Drug Kinetics; Evaluation; Extinction (Psychology); Fluorescence; Fluorescence Spectroscopy; Fostering; Generations; Head and Neck Cancer; Hemoglobin; Injection of therapeutic agent; Investigational Drugs; Investments; Kinetics; Laboratories; Lesion; Light; Link; Measurement; Measures; Metric; Mitochondria; Modeling; Monitor; Morphology; Mus; National Cancer Institute; Neoplasm Metastasis; Normal tissue morphology; Nuclear; Optical reporter; Optics; Outcome; Oxygen; Patients; Penetration; Performance; Phase; Phase I Clinical Trials; Photochemotherapy; Photosensitivity; Photosensitizing Agents; Physical condensation; Property; Public Health; Reporter; Reporting; Research; Research Personnel; Roswell Park Cancer Institute; Route; Series; Singlet Oxygen; Site; Skin; Solid Neoplasm; Spectrum Analysis; Staging; Swelling; System; T-Cell Lymphoma; Testing; Time; Tissues; Universities; absorption; base; clinically relevant; design; dosimetry; experience; fluorescence imaging; improved; in vivo; interest; intravenous administration; irradiation; light scattering; monolayer; neoplastic cell; nephelometry; phthalocyanine; pre-clinical; programs; quantum; research clinical testing; response; therapy outcome; treatment planning; tumor

DESCRIPTION (provided by applicant): PC 4 is a promising second generation photosensitizer for photodynamic therapy (PDT) that is now in Phase clinical trials for the treatment of cutaneous T cell lymphoma (CTCL), basal cell carcinoma (BCC) and cutaneous metastases. Other clinical trials are in early planning stages at Case Western Reserve University. PC 4 has excellent photophysical characteristics, including an intense extinction at 670 nm, where light penetration in tissue is efficient, and high singlet oxygen quantum yield. Biological responses to PC 4-PDT have been extensively characterized by researchers at Case with support of the National Cancer Institute. NCI also sponsored all of the preclinical IND (Investigational New Drug)-directed studies and provides GMP (Good Manufacturing Practices) PC 4 for the clinical trials. Thus, there has been a significant scientific and financial investment in PC 4. Initial experience in the Phase I trial has been positive, however it has also underscored the urgent need for optical dosimetry and monitoring in order to make rational treatment planning decisions. The outcome of PDT depends on the availability of sensitizer and light throughout the lesion, and the singlet oxygen mechanism of PC 4-PDT requires oxygen. None of these ingredients can be assumed and must therefore be measured directly or indirectly. Optical reporters of the deposition of photodynamic dose and/or biological response are also desirable. Special problems and opportunities present themselves in the particular case of PC 4. For example, because of its extremely high extinction at the treatment wavelength, PC 4 in the tissue may influence the transport of light. To address these dosimetry and monitoring issues in close connection to ongoing and planned clinical trials, we propose the following specific aims: (1) to construct and characterize an optical system capable of delivering PDT irradiation and performing, both fluorescence and reflectance spectroscopy in CTCL and BCC patients; (2) to evaluate the irradiation-induced increase in PC 4 fluorescence as a possible dose metric in vivo; (3) to evaluate light scattering as a means of reporting mitochondria! responses to PC 4-PDT in vivo; and (4) to investigate the kinetics and intratumor distribution of PC 4 following intratumor injection and to establish the efficacy of this route of administration. Relevance to public health: Photodynamic therapy is being tested for the treatment of several cutaneous diseases. Research proposed here will develop means for measuring the quantities that determine the outcome of this therapy. Results will contribute to the ongoing clinical trials.

描述（由申请人提供）：pc4是一种有前途的第二代光敏剂，用于光动力治疗（PDT），目前正处于治疗皮肤T细胞淋巴瘤（CTCL），基底细胞癌（BCC）和皮肤转移的临床试验阶段。凯斯西储大学的其他临床试验正处于早期规划阶段。pc4具有优异的光物理特性，包括670 nm的强消光，其中光在组织中的穿透效率高，单线态氧量子产率高。在国家癌症研究所的支持下，凯斯的研究人员对pc4 - pdt的生物学反应进行了广泛的研究。NCI还赞助了所有临床前新药研究，并为临床试验提供GMP（良好生产规范）。因此，在PC 4上进行了重大的科学和财政投资。I期试验的初步经验是积极的，但它也强调了迫切需要光学剂量测定和监测，以便做出合理的治疗计划决策。PDT的结果取决于整个病变的敏化剂和光的可用性，pc4 -PDT的单线态氧机制需要氧。这些成分都不能假设，因此必须直接或间接测量。光动力剂量和/或生物反应沉积的光学报告器也是需要的。在PC 4的特殊情况下，出现了特殊的问题和机会。例如，由于其在处理波长处具有极高的消光性，组织中的pc4可能会影响光的传输。为了解决这些与正在进行的和计划中的临床试验密切相关的剂量学和监测问题，我们提出了以下具体目标：(1)构建和表征一个能够在CTCL和BCC患者中提供PDT照射并执行荧光和反射光谱的光学系统；(2)评估辐照引起的pc4荧光增加作为体内可能的剂量指标；(3)评价光散射作为报道线粒体的手段！体内对pc4 - pdt的反应；(4)研究肿瘤内注射后pc4的动力学和肿瘤内分布，并确定这种给药途径的有效性。与公众健康相关：目前正在测试光动力疗法治疗几种皮肤疾病。这里提出的研究将开发出测量决定这种治疗结果的数量的方法。结果将有助于正在进行的临床试验。