Area B: Multi-Tracer Volumetric PET (MTV-PET) to Measure Tumor Glutamine and Glucose Metabolic Rates in a Single Imaging Session

B 区：多示踪体积 PET (MTV-PET) 在单次成像中测量肿瘤谷氨酰胺和葡萄糖代谢率

• 批准号: 9483034
• 负责人: JOEL S KARP
• 金额: $ 144.83万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9483034
• 关键词: 4D Imaging; Address; Agreement; Algorithms; Area; Biological Assay; Biology; Breast Cancer Patient; Cancer Biology; Cancer Diagnostics; Cancer Patient; Clinical; Clinical Data; Clinical Oncology; Clinical Research; Cluster Analysis; Consumption; Data; Data Set; Development; Diagnosis; Diagnostic; Dose; Emerging Technologies; Funding; Glucose; Glutaminase; Glutamine; Glycolysis; Goals; Half-Life; Heterogeneity; Hour; Human; Image; Image Analysis; Injection of therapeutic agent; Kinetics; Laboratories; Lactate Dehydrogenase; Machine Learning; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Metabolic; Metabolism; Methodology; Methods; Modeling; Molecular; Outcome; Patients; Phenotype; Positron-Emission Tomography; Process; Radiation exposure; Reference Standards; Research; Technology; Testing; Three-Dimensional Image; Time; Tissues; Tracer; Tumor Biology; Validation; Work; analytical method; anticancer research; base; cancer diagnosis; cancer imaging; clinical Diagnosis; cohort; diagnostic biomarker; genomic biomarker; glucose metabolism; high dimensionality; image reconstruction; imaging biomarker; in vivo; inhibitor/antagonist; malignant breast neoplasm; metabolic rate; method development; molecular imaging; novel; parametric imaging; personalized diagnostics; phenotypic biomarker; precision oncology; radiotracer; reconstruction; response; targeted treatment; technology development; therapeutic target; tumor; tumor heterogeneity; tumor metabolism; whole body imaging

Precision oncology places an increased demand on cancer diagnostics to characterize tumors at the time of diagnosis. Tissue diagnostics for precision oncology increasingly rely on multi-valent assays to characterize cancer biology and identify therapeutic targets. The power of molecular imaging for cancer diagnosis has been well demonstrated by [18F]fluorodexoyglucose positron emission tomography (FDG PET/CT), widely used in clinical oncology. PET tracers targeted to facets of tumor biology now enable multi-valent molecular imaging to identify therapeutic targets. Early studies show that combined tracer studies, commonly FDG plus a target- specific tracer, are highly predictive of tumor response to targeted therapy. However, emissions from different PET tracers are indistinguishable to a PET scanner, requiring separate imaging sessions on separate days for multiple 18F-based tracers (~ 2 hour half-life) in the same patient. This limits the clinical practicality of multi-tracer PET, and fails to exploit the full power of multi-tracer PET to quantify tumor in vivo biology and biologic heterogeneity for highly variable process such as cancer metabolism. We will overcome this limitation by taking advantage of recent developments in volumetric PET scanners, fast reconstruction, and 4D image analysis methods from our laboratories to develop Multi-Tracer Volumetric PET (MTV-PET) to generate multi-valent, quantitative biologic parametric images for two or more tracers in a single session to guide precision oncology and translational cancer biology research. As such, our proposed technology development project addresses a need, described under Priority Area B for “new capabilities for advancing precise clinical diagnosis of cancer patients”. Using methods developed in our laboratories, we now propose to integrate and enhance these methodologies to develop and validate Multi-Tracer Volumetric PET (MTV-PET) to generate quantitative biologic parametric images for two or more tracers in a single session. We will develop and test this approach for simultaneous glucose and glutamine metabolism imaging, with the goal of guiding metabolism-targeted therapy such as inhibitors of glutaminase (GLS) and lactate dehydrogenase (LDH). The project will focus on the technology developments (largely computational) that enable multi-tracer imaging. Ongoing and separately funded work on clinical studies will acquire data from two separate imaging PET sessions using current technology and will provide data for method development. We will first optimize tracer dose timing, image reconstruction, and image time binning for dual tracer MTV-PET (Aim 1), followed by implementation and technical validation of image analysis using a mixture analysis approach (Aim 2). This will set the stage for technical validation of MTV-PET (Aim 3) and an exploratory aim (Aim 4) testing image analytics based on machine learning. Successful completion of our technology development will yield a new method for multi-tracer PET that would change the landscape for cancer imaging diagnostic biomarker and precision oncology research, consistent with goals of RFA-CA-17-023 Priority Area B.

精确肿瘤学对癌症诊断提出了更高的要求，以在 诊断。精确肿瘤学的组织诊断越来越依赖于多价分析来表征 癌症生物学和确定治疗靶点。分子成像在癌症诊断中的力量一直是 [18F]氟代葡萄糖正电子发射断层扫描(FDG PET/CT)显示良好，广泛应用于 临床肿瘤学。针对肿瘤生物学各个方面的PET示踪剂现在使多价分子成像能够 确定治疗目标。早期研究表明，联合示踪剂研究，通常是FDG加上一个靶点- 特异性示踪剂，可高度预测肿瘤对靶向治疗的反应。然而，来自不同国家的排放 PET示踪剂对于PET扫描仪是难以区分的，需要在不同的日期进行单独的成像会话 同一患者体内的多个18F示踪剂(~2小时半衰期)。这限制了多重示踪剂的临床实用性。 PET，未能充分发挥多示踪PET对体内肿瘤生物学和生物学定量的能力 对于高度可变的过程，如癌症新陈代谢，异质性。我们将通过采取以下措施克服这一限制 体积PET扫描仪、快速重建和4D图像分析的最新发展优势 方法我们的实验室开发多示踪剂容量PET(MTV-PET)，以产生多价， 一次会议中用于两个或更多示踪剂的定量生物参数图像以指导精确肿瘤学 和转化型癌症生物学研究。因此，我们建议的技术开发项目旨在解决 需要，在优先领域B下描述为“推进癌症精确临床诊断的新能力” 病人“。使用我们实验室开发的方法，我们现在建议整合和增强这些 开发和验证多示踪剂容量PET(MTV-PET)以产生定量生物的方法学 单个会话中两个或更多跟踪器的参数图像。我们将为以下方面开发和测试此方法 同时进行葡萄糖和谷氨酰胺代谢成像，目的是指导新陈代谢靶向治疗 如谷氨酰胺酶(GLS)和乳酸脱氢酶(LDH)的抑制剂。该项目将重点放在 技术发展(主要是计算)，使多踪迹成像成为可能。持续的和单独的 资助的临床研究工作将从两个独立的成像PET会议上获取数据，使用Current 技术，并将为方法开发提供数据。我们将首先优化示踪剂剂量计时，图像 用于双示踪剂MTV-PET的重建和图像时间入库(目标1)，随后实施和 使用混合分析方法进行图像分析的技术验证(目标2)。这将为 MTV-PET(目标3)和探索性目标(目标4)测试图像分析的技术验证 机器学习。我们的技术开发的成功完成将产生一种新的多示踪剂方法 PET将改变癌症成像诊断生物标记物和精确肿瘤学研究的格局， 与RFA-CA-17-023优先领域B的目标一致。