EXPLORER: Changing the Molecular Imaging Paradigm with Total Body PET

EXPLORER：用全身 PET 改变分子成像范式

• 批准号: 9334154
• 负责人: RAMSEY D. BADAWI
• 金额: $ 313.81万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-25 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9334154
• 关键词: Adolescent; Anesthesia procedures; Antibodies; Arthritis; Biochemical; Biological; Biological Assay; Biological Process; Biomedical Research; Body Image; Body part; Brain; Cells; Chronic Disease; Clinic; Clinical; Clinical Research; Code; Computer Simulation; Dana-Farber Cancer Institute; Data; Development; Devices; Diabetes Mellitus; Diagnostics Research; Disease; Dose; Drug Kinetics; Ear; Electronics; Engineering; Ensure; Europe; Event; Funding; General Hospitals; Hospitals; Hour; Human; Human body; Image; Imaging Techniques; Immune system; Industry; Institution; Kinetics; Knowledge; Label; Letters; Location; Longitudinal Studies; Massachusetts; Measurement; Medical; Memorial Sloan-Kettering Cancer Center; Mental disorders; Metabolic syndrome; Methods; Micrometastasis; Modeling; Motion; Names; Noise; Nose; Obesity; Organ; Patients; Pediatrics; Pennsylvania; Performance; Pharyngeal structure; Physicians; Population; Positron-Emission Tomography; Process; Radiation; Radioisotopes; Research; Research Infrastructure; Risk; Scanning; Scientist; Services; Signal Transduction; Site; Sorting - Cell Movement; Systems Biology; Technology; Testing; Therapeutic; Time; Tissues; Tracer; United States National Institutes of Health; Universities; Vendor; Work; bioimaging; body system; clinical diagnostics; clinical practice; design; detector; drug discovery; image reconstruction; imaging agent; imaging capabilities; imaging scientist; imaging study; in vivo; innovation; insight; instrumentation; molecular imaging; nanomolar; novel therapeutics; professor; prototype; public health relevance; radiotracer; simulation; trafficking; uptake

 DESCRIPTION (provided by applicant): The key strength of positron emission tomography (PET) is its sensitivity that permits imaging of radiotracers in the sub-nanomolar concentration range. However, less than 1% of the available signal is captured, because only a small axial segment of the body (typically 15-20 cm) is imaged at any one time. This leads to relatively long imaging times and non-negligible radiation doses, which are major limiting factors in the broader application of PET. We have assembled a consortium to develop EXPLORER, the world's first total-body scanner that allows all the tissues and organs to be imaged simultaneously and will provide an effective sensitivity gain of at least a factor of 40 over current clinical PET/CT scanners. This sensitivity gain could be used to acquire 40-fold more signal (a >6-fold increase in signal-to-noise), or to acquire total-body images in 1/40th of the time or at 1/40th of the radiation dose, or to track biomolecules over 7-9 radionuclide half-lives (~16 hours for F-18 tracers, ~30 days for Zr-89 tracers) . This has profoundly transformative implications for the application of PET in both clinical diagnostics and research, for example, (1) the ability to acquire FDG whole- body studies in 15-30 seconds (breathhold-PET), (2) the ability to perform whole-body studies in dose- sensitive applications (e.g. pediatrics, adolescents, longitudinal studies of chronic disease and longitudinal studies of cell trafficking) at doses similar to those received on a round-trip transatlantic flight, and (3) the ability to do rapid kinetic studies and obtain pharmacokinetic data from all organs simultaneously as well as an image-derived input function, facilitating new drug discovery, studies of multi-organ interactions and systems biology. With previous NIH funding we have developed all the necessary building blocks for this scanner, including innovative detectors with time-of-flight and depth-encoding capability (essential for dealing with the parallax problems arising from recording highly oblique data), electronics, a complete in silico simulation of the scanner, and image reconstruction code. In this proposal, we seek to use the knowledge we have gained to build the first total-body PET scanner. The engineering work will be guided by industry leaders, and in parallel, our medical advisory board will ensure the proposed development is consistent with the performance needs for applications across a broad spectrum of disease states. The scanner will be sited at one of four top locations (U Penn, MSKCC, UC Davis or UCSF) that have the infrastructure to take advantage of the transformative opportunity presented by this unprecedented device.

 描述（由申请人提供）：正电子发射断层扫描 (PET) 的关键优势在于其灵敏度，允许对亚纳摩尔浓度范围内的放射性示踪剂进行成像，但是，捕获的可用信号不到 1%，因为只有很小的一部分。身体的轴向部分（通常为 15-20 厘米）在任意时间成像，这导致相对较长的成像时间和不可忽略的辐射剂量，这是更广泛应用的主要限制因素。我们组建了一个联盟来开发 EXPLORER，这是世界上第一台全身扫描仪，可以同时对所有组织和器官进行成像，并且与当前的临床 PET/CT 扫描仪相比，有效灵敏度至少提高 40 倍。这种灵敏度增益可用于获取 40 倍以上的信号（信噪比增加 >6 倍），或者以 1/40 的时间或以 1/40 的时间获取全身图像。 1/40 的辐射剂量，或追踪超过 7-9 个放射性核素半衰期的生物分子（F-18 示踪剂约为 16 小时，Zr-89 示踪剂约为 30 天），这对 PET 的应用具有深远的变革意义。例如，在临床诊断和研究中，(1) 在 15-30 秒内获得 FDG 全身研究的能力（屏气 PET），(2)在剂量敏感应用中进行全身研究（例如儿科、青少年、慢性病的纵向研究和细胞运输的纵向研究），剂量与跨大西洋往返航班所接受的剂量相似，并且（3）有能力同时获得所有器官的快速动力学研究和药代动力学数据以及图像衍生的输入功能，促进新药发现、多器官相互作用和系统生物学的研究。 利用之前的 NIH 资助，我们已经开发了该扫描仪的所有必要构建模块，包括具有飞行时间和深度编码功能的创新探测器（对于处理记录高度倾斜数据所产生的视差问题至关重要）、电子设备、完整的扫描仪的计算机模拟和图像重建代码在本提案中，我们寻求利用我们获得的知识来构建第一台全身 PET 扫描仪。工程工作将由行业领导者以及我们的领导者指导。医疗顾问委员会将确保拟议的开发符合广泛疾病状态的应用的性能需求，该扫描仪将位于四个拥有基础设施的顶级地点之一（宾夕法尼亚大学、MSKCC、加州大学戴维斯分校或加州大学旧金山分校）。这种前所未有的设备带来了变革性的机遇。