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.

为 4 种 PET 成像示踪剂开发完全自动化的质量控制程序，这将提高生产量并扩大患者可用的 PET 成像的多样性。

• 批准号: 9797682
• 负责人: Arkadij Elizarov
• 金额: $ 68.99万
• 依托单位: TRACE-ABILITY, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-08 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9797682
• 关键词: Acetone; Address; Aliquot; Alzheimer' s Disease; Amendment; Area; Automation; Benchmarking; Cardiology; Clinical; Clinics and Hospitals; Complex; Computer software; Contrast Media; Cyclotrons; Data; Detection; Development; Devices; Diagnostic; Dimethyl Sulfoxide; Disease; FDA approved; Future; Goals; Image; Imaging Techniques; Lead; Manuals; Methods; Molecular; Neurodegenerative Disorders; Neuroendocrine Tumors; Neurology; Output; Patients; Phase; Plant Roots; Positioning Attribute; Positron-Emission Tomography; Procedures; Process; Production; Quality Control; Radioactive; Radioisotopes; Radiopharmaceuticals; Reader; Risk; Rural; Sampling; Technology; Testing; Therapeutic; Time; Tissues; Tracer; Translating; Validation; Visual; Work; amyloid imaging; cGMP production; cancer imaging; clinical imaging; experience; imaging modality; improved; innovation; oncology; operation; protein biomarkers; rural area; sarcoma; skills; synergism; tau Proteins

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.

该项目的长期目标是提高正电子发射断层扫描 (PET) 的可用性 该方法的重点是消除复杂性和对不同疾病领域的患者进行成像。 与神经病学依赖的放射性造影剂、PET 示踪剂的生产相关的质量风险 该项目开发的具体解决方案是一个随后将提供的平台。 生产用于更多疾病领域的 PET 示踪剂也具有同样的优势。 PET 示踪剂依赖于半衰期较短的放射性核素，例如 F-18（110 分钟）、Ga-68（68 分钟） 分钟），必须通过回旋加速器或质量控制（QC）每天多次生产。 PET 示踪剂的生产是迄今为止 cGMP 生产过程中劳动力、技术和风险最密集的部分。 需要对 PET 示踪剂的 10-14 个不同参数进行评估才能发布供患者使用。 PET 示踪剂 QC 的复杂现状对 PET 成像的扩展构成了障碍，特别是 美国农村地区的小型医院和诊所通常会限制可生产的 PET 示踪剂的数量 在一个设施中，最终限制了 PET 成像对患者的可用性。 创新之处在于一次性套件，可以对单个样本进行多次测试 由酶标仪和自动移液器组成的平台已成功完成。 以 FDG（多种应用中最常用的 PET 示踪剂）为基准，它提供了以下结果： 该项目选择的四种 PET 示踪剂是：[F-] 18]Flobetaben – FDA 批准的 PET 示踪剂，用于阿尔茨海默病诊断中的淀粉样蛋白成像，[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 – 用于检测和治疗的领先标记物 肉瘤的管理，[Ga-68]DOTATATE – FDA 批准的用于神经内分泌肿瘤的 PET 示踪剂。 这项工作的影响将是：(1) 提高这 4 种 PET 示踪剂对患者的可用性，(2) 简化 未来示踪剂过渡到 Tracer-QC 平台的程序，以及 (3) 释放 PET 产能 生产设施在向成像中心提供的产品中添加更多 PET 示踪剂。 每个第一阶段的具体目标都侧重于 2 个风险最高的新测试之一。里程碑是实验性的。 演示所需的特定目标 1：丙酮（LOD = 2000 ppm）。 目标 2：DMSO（LOD = 2000 ppm）。II 期具体目标 1-4：使用新示踪剂的临床生产。 用于质量控制的示踪剂-QC 1 ([F-18]Flobetaben、2 ([F-18]Flortaucipir)、3 ([F-18]FMISO)、4 ([Ga- 68]DOTATATE)：里程碑是 (a) 为每个 PET 示踪剂 QC 验证示踪剂-QC 方法，以及 (b) 提交的 IND/NDA 修正案将产生经过验证的全自动 QC 解决方案， 降低了风险，并且可以通过 4 种新示踪剂的 DMF 交叉引用轻松实施。