Department of Molecular & Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.
Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11309-11314. doi: 10.1073/pnas.1710466114. Epub 2017 Oct 10.
New radiolabeled probes for positron-emission tomography (PET) are providing an ever-increasing ability to answer diverse research and clinical questions and to facilitate the discovery, development, and clinical use of drugs in patient care. Despite the high equipment and facility costs to produce PET probes, many radiopharmacies and radiochemistry laboratories use a dedicated radiosynthesizer to produce each probe, even if the equipment is idle much of the time, to avoid the challenges of reconfiguring the system fluidics to switch from one probe to another. To meet growing demand, more cost-efficient approaches are being developed, such as radiosynthesizers based on disposable "cassettes," that do not require reconfiguration to switch among probes. However, most cassette-based systems make sacrifices in synthesis complexity or tolerated reaction conditions, and some do not support custom programming, thereby limiting their generality. In contrast, the design of the ELIXYS FLEX/CHEM cassette-based synthesizer supports higher temperatures and pressures than other systems while also facilitating flexible synthesis development. In this paper, the syntheses of 24 known PET probes are adapted to this system to explore the possibility of using a single radiosynthesizer and hot cell for production of a diverse array of compounds with wide-ranging synthesis requirements, alongside synthesis development efforts. Most probes were produced with yields and synthesis times comparable to literature reports, and because hardware modification was unnecessary, it was convenient to frequently switch among probes based on demand. Although our facility supplies probes for preclinical imaging, the same workflow would be applicable in a clinical setting.
新型放射性标记探针用于正电子发射断层扫描(PET),使我们能够越来越多地回答各种研究和临床问题,并促进药物的发现、开发和临床应用。尽管生产 PET 探针需要高昂的设备和设施成本,但许多放射性药物和放射化学实验室都使用专用放射性合成仪来生产每种探针,即使设备大部分时间都处于闲置状态,也是为了避免因重新配置系统流路而从一种探针切换到另一种探针所带来的挑战。为了满足不断增长的需求,正在开发更具成本效益的方法,例如基于一次性“盒式组件”的放射性合成仪,这些方法无需重新配置即可在探针之间切换。然而,大多数基于盒式组件的系统在合成复杂性或可容忍的反应条件方面做出了牺牲,有些系统不支持定制编程,从而限制了它们的通用性。相比之下,ELIXYS FLEX/CHEM 基于盒式组件的合成仪的设计支持比其他系统更高的温度和压力,同时还便于灵活的合成开发。在本文中,我们将 24 种已知的 PET 探针的合成方法适用于该系统,以探索使用单个放射性合成仪和热室生产具有广泛合成需求的各种化合物的可能性,同时进行合成开发工作。大多数探针的产率和合成时间与文献报道相当,而且由于不需要硬件修改,因此根据需求频繁切换探针非常方便。尽管我们的设施提供用于临床前成像的探针,但相同的工作流程也适用于临床环境。