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，用于自动制备Ga-68标记的 在进行PET成像的任何部位使用药物。该设备正在开发，以支持更广泛的 Ga-68化合物在诊断PET成像中的创造、分配、研究和使用。 过去，全世界使用基于Ga-68的放射性药物的人数激增 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68 Ga-DOTATOC和相关的生长抑素受体结合肽， 最近，靶向前列腺癌的药物如PSMA-11，正在欧洲推动这种扩张， 预计美国也将出现类似的增长，DOTATOC在美国获得了孤儿药地位。 2013年FDA。然而，今天，美国只有少数几个学术网站提供所需的所有Ga-68药物 以满足患者需求，通常通过扩大研究性新药（IND）临床试验方案。 在许多情况下，使用Ga-68标记药物的PET成像是最好的可用诊断程序， 尽管这些新药物的使用对患者的疾病检测至关重要，但获得这些新药物的机会却很有限。 由于Ga-68的半衰期短（68分钟），现有的放射性药物网络（ 设计用于分配具有较长半衰期（>= 110分钟）的放射性药物）以递送Ga-68 药物有效。现场制备Ga-68药物的工作预计将随着这一分配而增加 问题. Five Eleven将通过一种不需要专业知识就能操作的设备来满足这种不断增长的需求 和维持，并使生产无菌的可注射Ga-68放射性标记药物的过程完全自动化。的 器械将基于行业标准、一次性使用组件，并且不会使用外部 连接的计算机或其他设备进行操作，因为它将没有可改变的操作参数。 我们的项目目标是：1）优化设备的操作参数，有效地减少 控制系统和硬件达到最低限度，与现有系统相比，成本显著降低（降低10倍） 系统.目标1将评估流体驱动压力/真空、流速和温度，以确定灵敏度 最终产物的产率和纯度与这些参数中的每一个的关系。2)开发全自动设备 基于最低硬件配置和固定控制系统;以及3）演示自动化 通过生产符合所有质量标准的3 Ga-68化合物P15-041、PSMA-11和DOTATOC， 根据FDA对可注射Ga-68标记药物的要求（pH、张力、放射化学纯度> 90%、放射化学纯度> 90%）， 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 第一阶段的完成将导致第二阶段设备的全面商业开发， 使用在临床PET成像站点生产的专利或通用新Ga-68药物的临床研究。 页1的1

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