Development of completely automated quality control procedures for 4 PET Imaging tracers that will increase production throughput and lead to expanded diversity of PET imaging available to patients.

该项目的长期目标是增加正电子发射断层扫描(PET)的可用性 为不同疾病地区的患者提供成像服务。该方法侧重于消除复杂性和 神经病学所依赖的PET示踪剂与放射性造影剂生产相关的质量风险 和肿瘤学。在此项目中开发的特定解决方案是一个平台，该平台将在之后交付 在扩大各种疾病领域使用的PET示踪剂的生产中也有同样的好处。 宠物示踪器依赖具有固有短半衰期的放射性核素，如F-18(110分钟)、Ga-68(68分钟) 分钟)，每天必须由回旋加速器或发电机产生多次。质量控制(QC) 到目前为止，PET示踪剂是cGMP生产过程中劳力、技能和风险最密集的部分。它 需要评估10-14个不同的参数，以使PET示踪剂释放供患者使用。这个 PET示踪剂QC的复杂电流状态阻碍了PET成像的扩展，特别是对 美国农村地区较小的医院和诊所经常限制可能生产的PET示踪剂的数量 在一个设施中，并最终限制了患者的PET成像的可用性。 创新之处在于一次性试剂盒，它可以对单个样本进行多项测试 由微量平板阅读器和自动移液器组成的平台。跟踪-QC已成功 以FDG为基准，FDG是用于多种应用的最常见的PET示踪剂。它已经交付了 所需的数据简化、效率和可追溯性。为该项目选择的四种PET示踪剂是：[F- 18.Florbetaben-FDA批准了用于阿尔茨海默病诊断的淀粉样蛋白成像的PET示踪剂[F- 18]Flortaucipir，一种对阿尔茨海默病和其他疾病具有最高预测潜力的tau蛋白标记物 神经退行性疾病，如TBI/CTE，[F-18]FMISO领先的检测和 肉瘤的管理，[Ga-68]DOTATE-FDA批准的神经内分泌肿瘤PET示踪剂。 这项工作的影响将是：(1)改善这4种PET示踪剂对患者的可用性，(2)简化 将未来的示踪剂转移到Tracer-QC平台的程序，以及(3)释放PET中的容量 生产设施，以增加更多的PET示踪剂，以提供给成像中心。 每个第一阶段的具体目标都集中在两个风险最高的新测试之一。里程碑是试验性的 对理想的检测极限进行演示。具体目标1：丙酮(LOD=2000ppm)。特定的 目的2：二甲基亚砜(LOD=2000ppm)。第二阶段具体目标1-4：使用新示踪剂的临床生产 跟踪--用于质量控制的QC。1([F-18]Florbetaben，2([F-18]Flortaucipir，3([F-18]FMISO)，4([Ga- (68)DOTATATE)：里程碑是(A)对每个PET示踪剂QC进行验证的示踪器-QC方法和(B) IND/NDA修正案提交。该项目将产生一个经过验证的全自动化质量控制解决方案， 降低了风险，便于使用DMF交叉参考4种新示踪剂。

Long-term objective of this project is increased availability of Positron Emission Tomography (PET) imaging to patients across different disease areas. The approach focuses on eliminating complexity and quality risks associated with production of radioactive contrast agents, PET tracers relied upon in neurology and oncology. The specific solution developed in this project is a platform that will afterwards deliver the same benefits in production of PET tracers used in an expanded variety of disease areas. PET Tracers rely on radionuclides with inherently short half-lives such as F-18 (110 min), Ga-68 (68 min), that have to be produced multiple times a day from a cyclotron or generator. Quality Control (QC) of PET tracers is by far the most labor-, skill- and risk-intensive part of the cGMP production process. It requires assessment of 10-14 different parameters for the PET tracer to be released for patient use. The complex current state of PET tracer QC presents a barrier to the expansion of PET imaging, particularly to smaller hospitals and clinics in the rural US, often limits the number of PET tracers that may be produced in one facility, and ultimately limits the availability of PET imaging to patients. The innovation is in the disposable kit that enables multiple tests from a single sample on a single platform composed of a microplate reader and automated pipettor. Tracer-QC has been successfully benchmarked with FDG, the most common PET tracer used in multiple applications. It has delivered the desired simplification, efficiency and traceability of data. Four PET tracers chosen for this project are: [F- 18]Florbetaben – FDA approved PET tracer for amyloid imaging in Alzheimer’s Disease diagnostics, [F- 18]Flortaucipir, – a tau protein marker with highest predictive potential for Alzheimer’s Disease and other neurodegenerative diseases such as TBI/CTE, [F-18]FMISO – leading marker for detection and management of sarcomas, [Ga-68]DOTATATE – FDA-approved PET tracer for neuroendocrine tumors. The impacts of this work will be: (1) improved availability of these 4 PET tracers to patients, (2) streamlined procedures for transition of future tracers onto Tracer-QC platform, and (3) freed up capacity in PET production facilities to add more PET tracers to their offerings to the imaging centers. Each Phase I Specific Aim focuses on one of 2 riskiest new tests. Milestone is experimental demonstration of the desired limit of detection. Specific Aim 1: Acetone (LOD = 2000 ppm). Specific Aim 2: DMSO (LOD = 2000 ppm). Phase II Specific Aims 1-4: Clinical Production of new tracer using Tracer-QC for quality control. 1 ([F-18]Florbetaben, 2 ([F-18]Flortaucipir, 3 ([F-18]FMISO), 4 ([Ga- 68]DOTATATE): Milestones are (a) Tracer-QC method validated for each PET tracer QC and (b) IND/NDA amendment filed. The project will yield a fully-automated QC solution that has been validated, de-risked and is positioned for easy implementation with DMF cross-reference for 4 new tracers.