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

描述(申请人提供)：分子成像涉及使用非侵入性技术来显示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不能提供有关癌症等疾病过程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了解和评估治疗反应，以及提供对靶向治疗效果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和生理成像是身体PET/CT成像项目的关键组成部分，因为基于相应CT扫描的感兴趣区分析对于准确量化示踪剂药效学和药代动力学至关重要，这对于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是必要的。这项提案要求提供资金，用于专门研究最先进的全身PET/CT扫描仪，适用于使用复杂的扫描方案和/或新的或寿命较短的PET放射性药物进行人体临床试验和研究中的动态成像。这将使定量成像生物标记物能够在肿瘤学、神经病学、血管和代谢疾病、移植科学、感染性和炎症性肺部疾病，包括艾滋病毒/艾滋病合并感染等广泛的病理学中描述疾病状态。重点放在对治疗早期反应的成像生物标记物评估上。通过促进适应性治疗试验的设计，更好地了解10个主要项目中提出的疾病的分子基础和早期生理变化，可望在患者个体化管理方面取得进展。项目目标包括疾病生理和药物靶标效应的具体测量，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未来的疾病管理方案和避免患者几周或几个月的毒性和无效治疗变得至关重要。目前，匹兹堡大学在所有科学和医学学科领域进行研究性PET/CT扫描的能力受到很大限制，因为在PET-回旋加速器设施或长老会医院综合体内或附近没有PET/CT扫描仪可用。此外，所有临床PET/CT扫描仪都在满负荷运行，没有专门的时间用于研究。此外，这款扫描仪将取代即将停止支持的HR+(仅限PET扫描仪)之一。因此，该仪器对正在进行的PET神经成像计划的成功至关重要。显然，匹兹堡大学目前和未来由NIH资助的研究人员需要最先进的PET/CT研究资源，以实现他们在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.