Multi-tracer PET Tumor Imaging

多示踪剂 PET 肿瘤成像

• 批准号: 8037722
• 负责人: Dan J Kadrmas
• 金额: $ 34.05万
• 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/8037722
• 关键词: Acetates; Algorithms; Animals; Biological Markers; Blood; Blood Volume; Blood flow; Blood specimen; Brain Neoplasms; Cancer Detection; Canis familiaris; Cell Proliferation; Clinical; Clinical Trials; Coupled; Data; Data Set; Development; Diagnostic Neoplasm Staging; Disease; Evaluation; Future; Glioma; Gold; Grant; Growth; Health; Histopathology; Hypoxia; Image; Imaging technology; Individual; Injection of therapeutic agent; Institution; Kinetics; Link; Lipids; Magnetic Resonance Imaging; 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; 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; 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目标进行成像。PET在癌症检测和分期方面的临床应用已经得到了很好的证实。成像代谢、增殖、血流和许多其他分子靶标的新示踪剂的发展为图像引导的个性化医学提供了几乎无限的潜力。然而，由于目前的技术一次只能对一种PET示踪剂进行成像，因此大部分潜力尚未实现，因为需要安排多次扫描，通常在不同的日期进行，从而导致成本高、图像对齐问题以及患者的漫长而繁重的体验。最近的进展表明，使用交错注射和动态成像，在一次扫描中成像2-3个PET示踪剂在技术上是可行的。每种示踪剂的测量可以使用基于每种示踪剂动力学约束的“信号分离”算法进行恢复。该项目将继续开发这种快速多示踪成像技术，重点是开发具有直接价值的具体方法，并将其转化为临床患者成像。将研究四种示踪剂：18f -氟脱氧葡萄糖（FDG）作为葡萄糖代谢的标记物；18f -氟胸苷（FLT）用于增殖；11c -乙酸酯（ACE）用于脂质合成和相关生长；15o -水（H2O）用于血流量和体积分布。目标1将开发和测试FDG、FLT和ACE单次扫描的快速双示踪剂和三示踪剂成像方法，目标是双示踪剂的总扫描时间约为70分钟，三示踪剂成像的总扫描时间为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算法，强调适合日常使用的鲁棒算法。快速多示踪成像也为确定相互关联的生理参数提供了独特的机会。目的3将研究测量肿瘤血液的方法，这些血液来源于所有示踪剂的第一次摄取，使用H2O PET作为流量的标准测量。这将有可能提供可靠的血流量测量，而不需要聚焦的血流量示踪剂。整个项目旨在将多示踪PET技术转化为临床肿瘤成像，这将通过Aim 4明确完成。20例原发性脑肿瘤患者将在任何治疗前、放化疗6周后和肿瘤复发时进行多示踪PET成像。这些数据将验证Aims 1-3的新方法，并将开始探索多示踪PET生物标志物在预测肿瘤侵袭性、为患者分配个性化治疗方案和评估治疗反应方面的临床价值。公共卫生相关性：癌症治疗的进步提供了大量的治疗药物、放射治疗和靶向药物，为治疗癌症提供了大量的武器。需要合理的方法来选择对每个患者最好的治疗方法，例如用正电子发射断层扫描（PET）进行肿瘤成像。本项目将开发新的和改进的方法，通过PET成像的多种示踪剂来表征肿瘤，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手段。