Measurement of Hypoxia in Non Small Cell Lung Carcinoma

非小细胞肺癌缺氧的测量

• 批准号: 6626273
• 负责人: MICHAEL J KELLEY
• 金额: $ 29.62万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626273
• 关键词: adduct; angiogenesis; apoptosis; biomarker; clinical research; clinical trial phase II; drug receptors; flow cytometry; human subject; human therapy evaluation; hypoxia; hypoxia inducible factor 1; imidazole; immunocytochemistry; keratin; neoplasm /cancer blood supply; neoplasm /cancer chemotherapy; nitro compounds; nonsmall cell lung cancer; patient oriented research; plasminogen activator inhibitors; positron emission tomography; receptor binding; vascular endothelial growth factors

DESCRIPTION (provided by applicant): Tumor hypoxia has been implicated as a prognostic marker in human tumors and may be a determinant of tumor response to both radiation and cytotoxic therapy. We propose a pilot phase II clinical trial to determine the safety and feasibility of measurement of tumor hypoxia in patients with non-small cell lung cancer (NSCLC) using the 2-nitroimidazole, EF5. Specific Aim 1: Measurement of hypoxia in NSCLC by EF5 binding. Patients with Stage I/II or Stage III will be administered EF5 prior to surgical biopsy or excision of tumor. Tumor samples will be examined for binding of EF5 to hypoxic areas. Tumor response will be ascertained for those patients with Stage III disease receiving chemotherapy/radiation. Tumor samples will be obtained from patients undergoing repeat tumor biopsy to assess longevity of EF5 adducts. Hypothesis: There is a range of tumor hypoxia in NSCLC that can be detected by EF5 binding. Specific Aim 2: Correlation of hypoxia measured by EF5 with biological markers of hypoxia. Hypoxia induces a number of biological responses mediated through HIF-1-controlled expression. Concurrent measurement of potential serum markers of hypoxia, tissue protein markers of hypoxia, tumor angiogenesis, and apoptosis will be performed to allow correlation with measurement of tumor hypoxia. Hypothesis: Hypoxia measured by EF5 binding in tumor tissues is correlated with biological markers of hypoxia in tumor and blood of patients with NSCLC. Specific Aim 3: Correlate tumor perfusion as measured by clinically applicable methods with hypoxia in patients with non-small cell lung cancer. Tumor hypoxia results from altered tumor blood flow. Advances in imaging techniques allows the non-invasive measurement of tumor blood flow in patients. We will use 150-water PET scanning to measure tumor blood flow and correlate these measurements with tumor hypoxia and each other. Hypothesis: Altered (reduced) tumor blood flow is associated with greater tumor hypoxia. We believe the data from this pilot study will be useful to design future study(ies) with clinical endpoints and to guide selection of subjects for novel hypoxia-directed therapies in patients with NSCLC.

描述（由申请人提供）：肿瘤缺氧已被认为是 人类肿瘤中的预后标志物，可能是肿瘤反应的决定因素 放射线和细胞毒性疗法。我们提出了一个飞行员II期临床 试验以确定肿瘤缺氧测量的安全性和可行性 在患有2-硝基咪唑的非小细胞肺癌（NSCLC）的患者中 EF5。特定目标1：通过EF5结合对NSCLC中缺氧的测量。患者 在手术活检之前，将使用I/II期或III期阶段III进行EF5 或切除肿瘤。将检查肿瘤样品的EF5结合 低氧区域。对于那些患有期的患者，将确定肿瘤反应 III疾病接受化学疗法/放射线。将获得肿瘤样品 从接受反复肿瘤活检的患者评估EF5的寿命 加合物。假设：NSCLC中有一系列肿瘤缺氧可以是 通过EF5结合检测。特定目标2：通过EF5测量的缺氧的相关性 与缺氧的生物标记。缺氧诱导许多生物学 通过HIF-1控制的表达介导的响应。并发测量 缺氧的潜在血清标记，缺氧的组织蛋白标记，肿瘤 血管生成和凋亡将允许与 肿瘤缺氧的测量。假设：通过EF5结合测量的缺氧 肿瘤组织与肿瘤中缺氧的生物学标志物相关， NSCLC患者的血液。特定目标3：将肿瘤灌注相关 通过临床适用的方法测量的患者 非小细胞肺癌。肿瘤缺氧导致肿瘤血液的改变 流动。成像技术的进步允许非侵入性测量 患者的肿瘤血流。我们将使用150种水PET扫描进行测量 肿瘤血流并将这些测量与肿瘤缺氧相关 其他。假设：改变（减少）肿瘤血流与 肿瘤缺氧更大。我们认为这项试验研究的数据将有用 设计具有临床终点的未来研究（IES），并指导选择 NSCLC患者的新型缺氧指导疗法的受试者。