Multi-tracer PET Tumor Imaging

描述(申请人提供)：正电子发射断层扫描(PET)的最大优点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。正电子发射计算机断层扫描在癌症检测和分期中的临床应用是公认的。用于新陈代谢、增殖、血流和众多其他分子靶点成像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，这一潜力仍有很大一部分尚未实现，因为目前的技术只允许一次只对一种PET示踪剂进行成像-需要安排多个扫描会话，通常是在不同的日期，这导致了高昂的成本、图像对齐问题以及患者漫长而繁重的体验。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。可以使用基于每个示踪剂的动力学约束的“信号分离”算法来恢复每个示踪剂的测量。该项目将继续开发这种快速多踪迹成像技术，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-脱氧葡萄糖(FDG)作为葡萄糖代谢的标志；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；以及15O-水(H2O)用于血流和分配容量。AIM 1将开发和测试在单次扫描中对FDG、Flt和ACE进行快速双示踪和三重示踪成像的方法，目标是总扫描时间约为70分钟。双示踪，90-120分钟。用于三重示踪成像。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。AIM 2将开发改进的多示踪算法，强调适合常规使用的健壮算法。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将研究使用H2O PET作为流量的标准测量方法，从所有存在的示踪剂的第一次通过摄取来测量肿瘤血液。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器。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名原发脑肿瘤患者将在任何治疗前、化疗和放射治疗后6周以及肿瘤复发时接受多示踪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生物标记物在预测肿瘤侵袭性、分配患者个性化治疗方案和评估治疗反应方面的临床价值。与公共健康相关：癌症治疗的进步提供了大量的治疗药物、放射治疗和靶向制剂，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来说最好的治疗方法，例如正电子发射断层扫描(PET)的肿瘤成像。该项目将开发新的和改进的方法，通过使用多种示踪剂的PET成像来表征肿瘤，为个别患者选择最佳治疗方案提供一种新的和极大改进的手段。

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.