Thinking inside the “box”: Development and implementation of a novel automated radiosynthesizer for 18F-labeled positron emission tomography tracers
Since the industrial revolution, automation has proven to be a vital component in the growth of any major industry. For positron emission tomography (PET), automation provides efficient, reproducible, and safe methods for routinely producing PET imaging agents, or tracers, using short lived radioisotopes. Over the years, many automated radiosynthesizers have been developed to automate the required production steps up through preparation of the tracer for intravenous injection into the patient or subject, both for clinical and preclinical applications. However, many commercial radiosynthesizers have temperature, pressure, and reagent compatibility limitations, which have required synthetic radiochemists to tailor and optimize synthesis protocols to fit within the constraints of a particular automated radiosynthesizer. Furthermore, the fluidic pathways on these systems generally need to be reconfigured for each tracer one wishes to make. To overcome these limitations, our group has developed a novel, three-reactor, automated radiosynthesizer (ELIXYS) based on the principle of dynamic fluid paths, which is achieved by actuating the reactors to different positions and pneumatically sealing them against a chemically inert gasket. The mechanism enables compatibility with high pressures and obviates the need for large numbers of pressure-limiting valves and fittings. Coupled with a chemist-friendly user interface, it also enables users to quickly automate known radiosyntheses and develop new protocols without requiring specific hardware modifications for each tracer. In this dissertation, I present the design, characterization, validation, and implementation of the system and discuss the capabilities, limitations, and overall work I performed with the system in automating 18F-labeled PET tracer radiosyntheses. I also include the translation of several known tracers onto the system, automation of tracers not previously automated, as well as characterization data helpful for others to more efficiently utilize this and other automated radiosynthesizers. Overall, radiosyntheses of 18F-labeled PET tracers performed on the ELIXYS resulted in similar or improved radiochemical yields and synthesis times compared to both automated and manual radiosyntheses, without the need for any hardware reconfiguration to make different tracers.