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

摘要： Five Eleven Pharma正在开发一种简单、低成本的设备，用于自动化制备Ga-68标记 任何进行正电子发射计算机断层扫描的地点的药物。该设备正在开发中，以支持更广泛的 诊断PET成像中Ga-68化合物的产生、分布、研究和使用 过去，以Ga-68为基础的放射性药物在世界各地的使用激增 几年，特别是在欧洲，那里大约有100个中心提供各种Ga-68调查剂。 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，在欧洲推动了很大一部分扩张， 在美国，DOTATOC获得了美国的孤儿药物地位，预计也会出现类似的增长 美国食品和药物管理局在2013年。然而，今天，美国只有几个学术网站提供了所需的所有基于Ga-68的药物 以满足患者的需求，通常是通过扩大研究新药(IND)临床试验方案。 在许多情况下，使用Ga-68标记药物进行PET成像是可用的最佳诊断方法 这些新药的使用受到限制，因为患者需要检测疾病。 由于Ga-68的半衰期很短(68分钟)，现有的放射性药物网络(即 是为分布半衰期更长(=110分钟)的放射性药物而设计的，以提供Ga-68 高效地使用药物。由于这种分布，预计Ga-68药物的现场制备将会增加 有问题。Five Eleven将通过一种几乎不需要专业知识就能操作的设备来满足这一日益增长的需求 和维护，并完全自动化生产无菌、可注射的Ga-68放射性标记药物的过程。这个 设备将基于行业标准的一次性使用组件，不会在外部使用 连接计算机或其他设备进行操作，因为它不会有可变的操作参数。 我们的项目目标是1)优化设备的运行参数，以有效地减少 控制系统和硬件最少，与现有的控制系统和硬件相比，显著降低了成本(降低了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 这些参数对最终产品的产量和纯度的影响。2)开发全自动化设备 基于最低硬件配置和固定控制系统；以及3)演示自动化 通过生产3种符合所有质量标准的Ga-68化合物P15-041、PSMA-11和DOTATOC FDA对注射用Ga-68标记药物的要求(pH、紧张度、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)。成功 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成像现场生产的专利或仿制新药进行的临床研究。 第1页，共1页

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