A low-cost automated Gallium-68 drug preparation device for diagnostic PET imaging

用于诊断 PET 成像的低成本自动化 Gallium-68 药物制备设备

• 批准号: 9347339
• 负责人: David Alexoff
• 金额: $ 22.5万
• 依托单位: FIVE ELEVEN PHARMA, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-02 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9347339
• 关键词: Cancer Patient; Chemicals; Clinical; Clinical Research; Clinical trial protocol document; Complex; Computers; Cyclic GMP; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Drug Compounding; Europe; FOLH1 gene; Filtration; Formulation; Funding; Future; Gallium; Generic Drugs; Goals; Growth; Half-Life; Heating; Industry Standard; Injectable; Investigation; Investigational Drugs; Label; Lead; Liquid substance; Malignant neoplasm of prostate; Materials Testing; Metastatic Neoplasm to the Bone; Orphan Drugs; Patient Care; Patients; Pennsylvania; Peptides; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phonation; Positron; Positron-Emission Tomography; Preparation; Process; Production; Radio; Radioisotopes; Radiopharmaceuticals; Reagent; Recruitment Activity; Regulation; Research; Site; Small Business Innovation Research Grant; Somatostatin Receptor; Sterility; System; Tablets; Telephone; Temperature; Testing; Time; United States; Universities; Vacuum; base; cost; design; human disease; meetings; novel; novel diagnostics; novel therapeutics; operation; pressure; prototype; radiochemical; receptor binding; response; success; targeted agent

Abstract: Five Eleven Pharma is developing a simple, low-cost device for automating the preparation of Ga-68 labeled drugs at any site that is performing PET imaging. The device is being developed to support the broader creation, distribution, research and use of Ga-68 compounds in diagnostic PET imaging. There has been a surge in the use of Ga-68-based radiopharmaceuticals throughout the world in the past several years, particularly in Europe where about 100 centers provide various Ga-68 investigational agents. The success of these drugs, first of 68Ga-DOTATOC and related somatostatin receptor binding peptides, and more recently agents targeting prostate cancer such as PSMA-11, is fueling much of this expansion in Europe, and similar growth is expected in the United States, where DOTATOC received orphan drug status by the US FDA in 2013. Today, however, only a few academic sites in the US provide all the Ga-68-based drugs needed to meet patient demand, often through expanded access Investigational New Drug (IND) clinical trial protocols. In many cases PET imaging with Ga-68 labeled drugs are the best available diagnostic procedure available to patients for the detection of disease, yet access to these new drugs is limited. Because of the short half-life (68 min) of Ga-68, it will be difficult for existing radiopharmacy networks (that were designed for distribution of radiopharmaceuticals with longer half-lives (>= 110 minutes)) to deliver Ga-68 drugs efficiently. On-site preparation of Ga-68 drugs is expected to grow in response to this distribution problem. Five Eleven will meet this growing demand through a device that will require little expertise to operate and maintain, and fully automates the process for producing a sterile, injectable Ga-68 radio-labeled drug. The device will be based on industry-standard, single-use disposable components and will use no externally connected computer or other device to operate since it will have no changeable operating parameters. Our aims for the project are to 1) optimize the operating parameters of the device to effectively reduce the control system and hardware to bare minimums reducing cost significantly (by 10 X) compared to existing systems. Aim 1 will evaluate fluid drive pressure/vacuum, flow rate and temperature to establish the sensitivity of the yield and purity of the final product to each of these parameters. 2) Develop a fully automated device based upon a minimum hardware configuration and fixed control system; and 3) Demonstrate an automated system by producing 3 Ga-68 compounds P15-041, PSMA-11 and DOTATOC that meet all the quality criteria required by the FDA for injectable Ga-68 labeled drugs (pH, tonicity, radiochemical purity >90%, radiochemical identity, Ge-68 content < 0.001%, radionuclidic purity, radionuclidic identity and sterility). Successful completion of this phase I will lead to full commercial development of a device in phase II with testing in a clinical study using either proprietary or generic new Ga-68 drugs produced at the clinical PET imaging site. Page 1 of 1

抽象的： 5-11 Pharma 正在开发一种简单、低成本的设备，用于自动制备 Ga-68 标记的药物 在任何进行 PET 成像的部位使用药物。该设备的开发是为了支持更广泛的 Ga-68 化合物在诊断 PET 成像中的创造、分布、研究和使用。 过去，全球范围内基于 Ga-68 的放射性药物的使用激增 几年来，特别是在欧洲，大约有 100 个中心提供各种 Ga-68 研究药物。 这些药物的成功，首先是 68Ga-DOTATOC 和相关的生长抑素受体结合肽，以及 最近针对前列腺癌的药物，如 PSMA-11，正在很大程度上推动了欧洲的这种扩张， 预计美国也会出现类似的增长，DOTATOC 已获得美国孤儿药地位 2013 年获得 FDA 批准。然而，如今，美国只有少数学术机构提供所需的所有 Ga-68 药物 为了满足患者需求，通常通过扩大研究性新药 (IND) 临床试验方案的访问范围。 在许多情况下，使用 Ga-68 标记药物进行 PET 成像是目前可用的最佳诊断程序。 患者需要检测疾病，但获得这些新药的机会有限。 由于 Ga-68 的半衰期短（68 分钟），现有的放射性药物网络（即 设计用于分配半衰期较长（>= 110 分钟）的放射性药物，以输送 Ga-68 药物有效。 Ga-68 药物的现场制备预计将随着这种分布而增长 问题。 5-11 将通过一种无需太多专业知识即可操作的设备来满足这一不断增长的需求 并维护并完全自动化生产无菌注射用 Ga-68 放射性标记药物的过程。这 设备将基于行业标准的一次性组件，并且不会使用外部 连接计算机或其他设备进行操作，因为它没有可更改的操作参数。 我们该项目的目标是1）优化装置的运行参数，有效降低 控制系统和硬件达到最低限度，与现有的相比，显着降低成本（降低 10 倍） 系统。目标 1 将评估流体驱动压力/真空、流量和温度以确定灵敏度 最终产品的收率和纯度与每个参数的关系。 2）开发全自动装置 基于最小的硬件配置和固定的控制系统； 3) 展示自动化 系统生产符合所有质量标准的 3 种 Ga-68 化合物 P15-041、PSMA-11 和 DOTATOC FDA要求注射用Ga-68标记药物（pH、张力、放射化学纯度>90%、放射化学 同一性、Ge-68 含量 < 0.001%、放射性核素纯度、放射性核素同一性和无菌性）。成功的 第一阶段的完成将导致第二阶段设备的全面商业开发，并在 使用在临床 PET 成像站点生产的专有或通用新 Ga-68 药物进行的临床研究。 第 1 页，共 1 页