Production of diverse PET probes with limited resources: 24 18F-labeled compounds prepared with a single radiosynthesizer

Significance Molecular imaging with PET can provide a dynamic, whole-body picture of the rate of biological processes or distribution of biological targets by tracking the distribution of radiolabeled molecules or particles in the body over time. Continual efforts to develop new PET probes are expanding the variety of processes and targets that can be visualized, facilitating basic research, drug development, and patient care. However, access to these probes at all stages of their development is hindered by high costs arising, in large part, from the significant resources that are typically dedicated to production of a single probe. Emerging technologies with increased synthesis flexibility are allowing increased probe diversity with fewer resources and could significantly increase access to new molecular imaging agents. 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.