Pilot--Quantitation of tumor parameters by PET

Pilot--PET定量肿瘤参数

• 批准号: 6563969
• 负责人: NIZAR A MULLANI
• 金额: $ 29.68万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563969
• 关键词: angiogenesis; angiogenesis inhibitors; bioimaging /biomedical imaging; biomedical automation; blood flow measurement; computer assisted medical decision making; cooperative study; drug screening /evaluation; human subject; neoplasm /cancer blood supply; patient oriented research; positron emission tomography

Description: (provided by applicant) Measurement of tumor blood flow and metabolism by non-invasive methods, such as PET , is key to following the effect of antiangiogenic treatment in tumors. Preliminary results obtained by PET in our phase I study of antiangiogenic treatment with Endostatin, have yielded two critical pieces of information. The first is that at low doses of Endostatin (<60 mg/meter squared), both blood flow and glucose metabolism are increased as a function of time. At higher doses (>120 mg/meter squared), there is a clear reduction of blood flow to le tumors but an increase in glucose metabolism. These results suggest that blood flow decrease may precede metabolism decrease in antiangiogenic treatment of tumors and that tumor blood flow and glucose metabolism become uncoupled under moderately ischemic conditions. The second is that tumors can change in size, shape, and distribution, very rapidly. The imaged lesions are heterogeneous in blood flow and metabolism and therefore an accurate measure of these crucial parameters will require the development of new and automated methods of data analysis that are more sensitive and reproducible. Based on these issues, our Specific Aims in this Developmental Project are: (1) To define the parameters that will provide insight into the sequential changes occurring in blood flow and metabolism in tumors following therapy with antiangiogenic agents. (2) To develop methods and software tools to automatically extract this information from serial PET images of human tumors with emphasis on reproducibility and accuracy. (3) To validate these methods using data from a phase I trial of Endostatin; with subsequent application to other early clinical trials of putative antiangiogenic therapies such as PKI166 (Core D) and SU6668 (Developmental Project 4) The short-term significance of this Developmental Project is that these new and automated methods will shorten the time required for early clinical testing of new antiangiogenic agents. The long-term significance of this project is that these tools may eventually be used in patients to accurately predict antiangiogenic effects on tumors thereby optimizing anticancer effects.

说明：（申请人提供） 通过非侵入性方法测量肿瘤血流和代谢，例如 如PET，是跟踪肿瘤中抗血管生成治疗效果的关键。 在我们的抗血管生成I期研究中通过PET获得的初步结果 用内皮抑素治疗，已经产生了两个关键的信息。 第一个是在低剂量的内皮抑制素（<60 mg/m2）下， 血流量和葡萄糖代谢作为时间的函数而增加。在 较高剂量（>120 mg/m2），血流量明显减少 但会增加葡萄糖代谢。这些结果表明 血流减少可能先于抗血管生成药物代谢减少 肿瘤的治疗和肿瘤血流和葡萄糖代谢变得 在中度缺血条件下解偶联。第二，肿瘤可以 尺寸形状和分布的变化非常迅速成像的病变是 因此是一种准确测量 这些关键参数将需要开发新的自动化 数据分析方法更加灵敏和可重复。基于 这些问题，我们在这个发展项目的具体目标是： (1)为了定义将提供对序列的深入了解的参数， 治疗后肿瘤血流和代谢发生的变化 抗血管生成剂 (2)开发方法和软件工具来自动提取这些信息， 来自人类肿瘤的系列PET图像的信息，重点是 重复性和准确性。 (3)使用内皮抑素I期试验的数据验证这些方法; 随后应用于其他早期临床试验， 抗血管生成疗法，如PKI 166（核心D）和SU 6668（开发 项目4） 这个发展项目的短期意义是，这些新的 自动化方法将缩短早期临床所需的时间， 测试新的抗血管生成剂。这件事的长远意义 这些工具最终可能会用于患者， 预测对肿瘤的抗血管生成作用，从而优化抗癌 方面的影响.