EXPLORER: Changing the Molecular Imaging Paradigm with Total Body PET

 描述(由申请人提供)：正电子发射断层扫描(PET)的关键优点是其灵敏度，允许在亚纳米摩尔浓度范围内对放射性示踪剂成像。然而，只有不到1%的可用信号被捕获，因为一次只对身体的一小段轴向(通常是15-20厘米)进行成像。这导致了相对较长的成像时间和不可忽视的辐射剂量，这是PET更广泛应用的主要限制因素。我们已经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，并将提供至少40倍于当前临床PET/CT扫描仪的有效灵敏度增益。这种灵敏度提高可用于获取40倍以上的信号(信噪比增加6倍)，或在1/40的时间或1/40的辐射剂量下获取全身图像，或在7-9个放射性核素半衰期内跟踪生物分子(F-18示踪剂约16小时，锆-89示踪剂约30天)。这对PET在临床诊断和研究中的应用具有深远的变革意义，例如，(1)能够在15-30秒内获得FDG全身检查(屏气-PET)，(2)能够在剂量敏感的应用(例如儿科、青少年、慢性病的纵向研究和细胞贩运的纵向研究)中以与在跨大西洋往返飞行上接收的剂量相似的剂量执行全身检查，以及(3)能够进行快速动力学研究并同时从所有器官获得药代动力学数据以及图像导出的输入功能，从而促进新药的发现，多器官相互作用和系统生物学的研究。 利用NIH之前的资金，我们已经开发了这款扫描仪的所有必要组件，包括具有飞行时间和深度编码能力的创新探测器(对于处理因记录高度倾斜的数据而产生的视差问题至关重要)、电子设备、扫描仪的完整电子模拟和图像重建代码。在这项提议中，我们寻求使用我们所获得的知识来建造第一台全身PET扫描仪。工程工作将由行业领导者指导，同时，我们的医疗顾问委员会将确保拟议的开发与各种疾病州的应用程序的性能需求保持一致。扫描仪将安装在四个顶级地点(宾夕法尼亚大学、密歇根州立大学、加州大学戴维斯分校或加州大学旧金山分校)之一，这些地点拥有基础设施，可以利用这一史无前例的设备带来的变革性机遇。

 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.