PET/CT for quantitative biomarker assessment of disease & early therapy response

描述（由申请人提供）：分子成像涉及使用非侵入性技术来证明和评估作为疾病基础的异常生化过程和病理生理变化的程度。CT和标准MRI无法提供有关疾病过程（如癌症）的潜在生化和生理特性的信息。使用新型示踪剂的定量PET/CT非常适合于提供对疾病生物化学的更基本的理解和评估治疗反应，以及提供对靶向治疗疗效和新型示踪剂开发的见解。使用选择性开发的示踪剂的全身相关解剖学和生理学成像是身体PET/CT成像项目的关键成分，因为基于相应CT扫描的感兴趣区域分析对于示踪剂药效学和药代动力学的准确定量是必不可少的，所述示踪剂药效学和药代动力学是提供与基于组织和血清的疾病生物标志物的有意义的比较所必需的。该提案要求提供资金，用于专用研究全身最先进的PET/CT扫描仪，适用于在人体临床试验和研究中使用复杂的扫描协议和/或新型或短寿命PET放射性药物进行动态成像。这将允许在肿瘤学、神经学、血管和代谢疾病、移植科学、感染性和炎性肺部疾病（包括HIV/AIDS合并感染）的广泛病理学中对疾病状态进行定量成像生物标志物表征。重点放在对治疗的早期反应的成像生物标志物评估上。更好地了解10个重大项目中提出的疾病的分子基础和早期生理变化，预计将通过促进适应性治疗试验的设计，促进个体化患者管理的进步。项目目标包括疾病生理学和药物靶向效应的具体测量，提供疾病对药物反应的最早指标。用于早期疾病检测和治疗评估的定量成像的发展对于未来的疾病管理方案变得至关重要，并且使患者免于数周或数月的毒性和无效治疗。目前，在匹兹堡大学的所有科学和医学学科领域进行研究PET/CT扫描的能力受到极大的阻碍，因为PET回旋加速器设施内或附近或长老会医院综合体没有PET/CT扫描仪可供使用。此外，所有临床PET/CT扫描仪都在充分发挥临床能力，没有专门的时间用于研究。此外，该扫描仪将取代即将停止支持的HR+（仅PET扫描仪）。因此，该仪器成为成功的正在进行的PET神经成像程序的关键。很明显，匹兹堡大学目前和未来的NIH资助的研究人员需要最先进的PET/CT研究资源，以实现各自生物医学领域的科学目标。

DESCRIPTION (provided by applicant): Molecular imaging involves the use of noninvasive techniques to demonstrate and assess the extent of abnormal biochemical processes and pathophysiological changes that are the basis of disease. CT and standard MRI cannot provide information on the underlying biochemical and physiological properties of disease processes such as cancer. Quantitative PET/CT using novel tracers is ideally suited to provide a more fundamental understanding of disease biochemistry and assess therapy response as well as providing insights on targeted therapy efficacy and novel tracer development. Whole body correlative anatomic and physiological imaging using selectively developed tracers is a critical ingredient for body PET/CT imaging projects since region-of-interest analysis based on a corresponding CT scan is essential for accurate quantification of tracer pharmacodynamics and pharmacokinetics necessary to provide a meaningful comparison with tissue and serum-based biomarkers of disease. This proposal requests funds for a dedicated research whole-body state-of-the-art PET/CT scanner suitable for conducting dynamic imaging in human clinical trials and research studies using sophisticated scanning protocols and/or novel or short lived PET radiopharmaceuticals. This will allow quantitative imaging biomarker characterization of disease states in a wide range of pathologies in oncology, neurology, vascular and metabolic disease, transplant science, infectious and inflammatory pulmonary diseases, including HIV/AIDS co-infection. Emphasis is placed on imaging biomarker assessment of early response to therapy. A better understanding of the molecular basis and early physiological changes in the diseases presented in the 10 Major Projects are expected to result in advances in individualized patient management by promoting the design of adaptive therapy trials. Project goals include specific measurements of disease physiology and drug-target effects giving the earliest indicator of disease response to drug. Development of quantitative imaging for early disease detection and therapy assessment is becoming critical to future disease management protocols and spare patients weeks or months of toxicity and ineffective treatment. Currently, the capability of performing research PET/CT scans across all scientific and medical discipline areas at the University of Pittsburgh is greatly hampered because no PET/CT scanner is available for use in or near the PET-Cyclotron Facility or at the Presbyterian Hospital complex. Furthermore, all clinical PET/CT scanners are operating at full clinical capacity, with no dedicated time available for research studies. In addition, this scanner will replace one of the HR+ (PET only scanners) soon to be out of support. Thus this instrument becomes critical to the success of the ongoing PET neuroimaging program. It is clear that a state-of-the-art PET/CT research resource is needed by current and future NIH funded investigators at the University of Pittsburgh to achieve their scientific goals in their respective biomedical fields.