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： 五十一制药正在开发一种简单的低成本设备，用于自动化标记的GA-68 任何正在执行宠物成像的站点的药物。正在开发该设备以支持更广泛的 诊断宠物成像中GA-68化合物的创建，分布，研究和使用。 过去，全世界在全球使用基于GA-68的放射性药物的使用激增 几年，尤其是在欧洲，大约100个中心提供了各种GA-68研究代理商。 这些药物的成功，第一个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（例如PSMA-11）的特工正在加剧欧洲的大部分扩张， 在美国，DoTATOC获得了美国的孤儿状态，预计将在美国进行类似的增长 FDA在2013年。但是，今天，美国只有少数几个学术网站提供所有基于GA-68的药物 为了满足患者的需求，通常通过扩大的访问研究新药（IND）临床试验方案。 在许多情况下，使用GA-68标记药物的PET成像是可用 检测疾病的患者，但是使用这些新药的患者受到限制。 由于GA-68的半衰期短（68分钟），因此现有的放射性药物网络将很难 设计用于分布较长半衰期（> = 110分钟）的放射性药物以提供GA-68 有效的药物。预计GA-68药物的现场制备将会因这种分布而增长 问题。五十一人将通过一种不需要几乎需要专业知识的设备来满足这一不断增长的需求 并维护，并充分自动化生产无菌注射的GA-68无线电标记药物的过程。这 设备将基于行业标准，一次性一次性零件，并且不会在外部使用 连接的计算机或其他设备要操作，因为它不会具有可变的操作参数。 我们对项目的目标是1）优化设备的操作参数，以有效地减少 与现有 系统。 AIM 1将评估流体驱动压力/真空，流速和温度以建立灵敏度 最终产品对每个参数的产量和纯度。 2）开发全自动设备 基于最小硬件配置和固定控制系统； 3）展示自动化 通过生产3种GA-68化合物P15-041，PSMA-11和DOTATOC，符合所有质量标准 FDA需要注射的GA-68标记药物（pH，tonicity，放射化学纯度> 90％，放射化学 身份，GE-68含量<0.001％，放射性核素纯度，放射性核素身份和不育）。成功的 该阶段的完成I将导致II阶段设备的全面商业开发，并在 临床研究使用临床宠物成像部位生产的专有或通用新的GA-68药物。 第1页，共1页