Multi-tracer PET Tumor Imaging

多示踪剂 PET 肿瘤成像

• 批准号: 7582583
• 负责人: Dan J Kadrmas
• 金额: $ 37.19万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7582583
• 关键词: Acetates; Algorithms; Animals; Binding; Biological Markers; Blood; Blood flow; Blood specimen; Brain Neoplasms; Cancer Detection; Canis familiaris; Cell Proliferation; Clinical; Clinical Trials; Coupled; Data; Data Set; Development; Disease; Evaluation; Future; Glioma; Gold; Grant; Growth; Histopathology; Hypoxia; Image; Imaging technology; Individual; Injection of therapeutic agent; Institution; Kinetics; Link; Lipids; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Medicine; Metabolism; Methodology; Methods; Microspheres; Modeling; Molecular; Molecular Target; Outcome; Patients; Performance; Perfusion; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physiological; Population; Positron-Emission Tomography; Primary Brain Neoplasms; Process; Protocols documentation; Radiation; Radiolabeled; Recovery; Recurrence; Relative (related person); Research; Residual Tumors; Running; Scanning; Schedule; Science; Signal Transduction; Simulate; Staging; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Tracer; Translating; Translations; Treatment Protocols; Water; Work; base; blind; cancer imaging; cancer therapy; clinical practice; cost; design; experience; fluorodeoxyglucose; glucose metabolism; imaging modality; improved; in vivo; insight; neoplasm imaging; new technology; patient population; public health relevance; radiotracer; rapid technique; response; simulation; standard measure; tumor; uptake; weapons

DESCRIPTION (provided by applicant): One of the greatest strengths of positron emission tomography (PET) is the ability to image any of a number of molecular or physiologic targets using different radiotracers. The clinical utility of PET is well- established for cancer detection and staging. The development of new tracers for imaging metabolism, proliferation, blood flow and numerous other molecular targets offers almost unlimited potential for image- guided personalized medicine. However, much of this potential remains unrealized because current technology permits only one PET tracer to be imaged at a time-multiple scanning sessions need to be scheduled, often on different days, resulting in high costs, image alignment issues, and a long and onerous experience for the patient. Recent advances have shown that it is technically feasible to image 2-3 PET tracers in a single scan using staggered injections and dynamic imaging. Measures of each tracer can be recovered using "signal-separation" algorithms based on kinetic constraints for each tracer. This project will continue development of such rapid multi-tracer imaging technologies, with emphasis on developing specific methods of immediate value and translation to clinical patient imaging. Four tracers will be studied: 18F-fluorodeoxyglucose (FDG) as a marker for glucose metabolism; 18F-fluorothymidine (FLT) for proliferation; 11C-acetate (ACE) for lipid synthesis and related growth; and 15O-water (H2O) for blood flow and volume of distribution. Aim 1 will develop and test methods for rapid dual- and triple-tracer imaging of FDG, FLT, and ACE in a single scan, targeting total scan times of ~70 min. for dual-tracer, and 90-120 min. for triple-tracer imaging. These methods will be evaluated in large animal tumor models and in patients with primary brain tumors. Aim 2 will develop improved multi-tracer algorithms, emphasizing robust algorithms suitable for routine use. Rapid multi-tracer imaging also provides unique opportunities for determining inter-linked physiologic parameters. Aim 3 will investigate methods of measuring tumor blood from derived from the first-pass uptake of all tracers present, using H2O PET as the standard measure of flow. This will potentially provide reliable measures of blood flow without the need for a focused blood flow tracer. The overall project is designed to translate multi-tracer PET technologies to clinical tumor imaging, which will be expressly accomplished through Aim 4. Twenty patients with primary brain tumors will undergo multi-tracer PET imaging prior to any therapy, after 6 weeks chemoradiotherapy, and at the time of tumor recurrence. These data will validate the new methods of Aims 1-3, and will begin to explore the clinical value of multi-tracer PET biomarkers for predicting tumor aggressiveness, assigning patients to personalized treatment regimens, and assessing response to therapy. PUBLIC HEALTH RELEVANCE: Advances in cancer treatment have provided a host of therapeutic drugs, radiation treatments, and targeted agents that provide a vast array of weapons for treating cancer. Rational methods are needed for selecting which treatment will be the best for each individual patient, such as tumor imaging with positron emission tomography (PET). This project will develop new and improved methods of characterizing tumors by PET imaging with multiple tracers, providing a new and greatly improved means of selecting the best treatment option for individual patients.

描述（由申请人提供）：正电子发射断层扫描（PET）的最大优势之一是能够使用不同的放射性示踪剂对许多分子或生理靶点进行成像。PET在癌症检测和分期方面的临床应用已得到充分证实。用于成像代谢、增殖、血流和许多其他分子靶点的新示踪剂的开发为图像引导的个性化医学提供了几乎无限的潜力。然而，这种潜力中的大部分仍然没有实现，因为当前技术仅允许一次对一种PET示踪剂进行成像-需要安排多个扫描会话，通常在不同的日子，导致高成本、图像对准问题以及患者的长期和繁重的经历。最近的进展表明，使用交错注射和动态成像在单次扫描中对2-3个PET示踪剂进行成像在技术上是可行的。每个示踪剂的测量可以使用基于每个示踪剂的动力学约束的“信号分离”算法来恢复。该项目将继续开发这种快速多示踪剂成像技术，重点是开发具有即时价值的具体方法，并将其转化为临床患者成像。将研究四种示踪剂：18 F-氟脱氧葡萄糖（FDG）作为葡萄糖代谢的标志物; 18 F-氟胸苷（FLT）用于增殖; 11 C-乙酸盐（ACE）用于脂质合成和相关生长; 15 O-水（H2O）用于血流量和分布容积。目标1将开发和测试单次扫描中FDG、FLT和ACE的快速双示踪剂和三示踪剂成像的方法，目标是双示踪剂的总扫描时间约为70分钟，三示踪剂成像为90-120分钟。这些方法将在大型动物肿瘤模型和原发性脑肿瘤患者中进行评估。目标2将开发改进的多示踪剂算法，强调适用于日常使用的鲁棒算法。快速多示踪剂成像还为确定相互关联的生理参数提供了独特的机会。目的3将研究使用H2O PET作为流量的标准测量方法，测量来自所有示踪剂的首过摄取的肿瘤血液。这将潜在地提供可靠的血流测量，而不需要聚焦的血流示踪剂。整个项目旨在将多示踪剂PET技术转化为临床肿瘤成像，这将通过Aim 4明确实现。20例原发性脑肿瘤患者将在任何治疗前、6周放化疗后和肿瘤复发时接受多示踪剂PET成像。这些数据将验证目标1-3的新方法，并将开始探索多示踪剂PET生物标志物用于预测肿瘤侵袭性、为患者分配个性化治疗方案和评估对治疗的反应的临床价值。公共卫生相关性：癌症治疗的进展提供了许多治疗药物、放射治疗和靶向药物，这些药物为治疗癌症提供了大量武器。需要合理的方法来选择哪种治疗方法对每个患者来说是最好的，例如正电子发射断层扫描（PET）肿瘤成像。该项目将开发新的和改进的方法，通过多种示踪剂的PET成像来表征肿瘤，为个体患者选择最佳治疗方案提供一种新的和大大改进的方法。