Abstract 5746: ARC-P HS+: A versatile radiosynthesizer for the production of PET tracers

Abstract

Abstract Objective: Positron Emission Tomography (PET) has seen dramatic growth in research over the last 20 years, and is now a standard in the diagnosis, staging, and treatment monitoring of cancer. PET uses molecular probes in trace amounts to examine specific biochemical, biological, and pharmaceutical processes noninvasively with high sensitivity, and has the advantage that the same probe can be used across cell cultures, mouse models, and patients. Although the majority of clinical PET studies are performed with 2-[F-18]fluoro-2-deoxy-D-glucose ([F-18]FDG), FDG-PET does not identify the specific biochemical pathways through which disease is occurring nor can it provide a companion diagnostic for the discovery, development, and use of molecular therapeutics. New technologies are needed to accelerate the development, production, and distribution of novel PET probes to increase the sophistication of cancer care through personalized medicine. Methods: The ARC-P HS+ radiosynthesizer was developed to address limitations in other synthesizers that restrict the diversity of probes they can produce. The ARC-P HS+ contains three reaction vessels that are moved among dedicated stations for reagent addition, sealed reaction, evaporation, and transfer, eliminating exposure of tubing and valves to high pressures, the root cause of limitations in other systems. It was designed to handle a wide range of synthesis conditions, including multiple reaction vessels, reagents that are corrosive or sensitive to the environment and reaction steps performed at high temperatures (e.g., up to 165C) and pressures (e.g. >100 psig [690 kPag]). To ensure ease of setup and diversity of probes, reagents are installed via a disposable cassette, which contains all wetted paths. Each cassette comprises reagent storage vials, gaskets for sealing the reaction vial, purification cartridges, and disposable valves. Results: Compared to our first generation synthesizer, the cassette-based approach of ARC-P HS+ reduced the number of reagents prepared and installed by the operator and eliminated the need for cleaning. Setup time and manual interventions were reduced. We confirmed that ARC-P HS+ could complete the demanding synthesis of [F-18]FAC, a novel probe for oncology, as well as [F-18]FMAU. Performance of both syntheses was comparable to previous reports. Conclusions: ARC-P HS+ is capable of producing the [F-18]FAC family of probes as well as probes with similar stringent synthesis requirements. Commercialization of this system with disposable cassette-based kits could facilitate production of these tracers, as well as providing a path to make other probes currently used in the clinic ([F-18]FDG, [F-18]FLT, [F-18]F-DOPA, etc.) more readily available. With minimal modifications in only software and reagents, this unit can be used to produce essentially all classes of F-18 labeled probes involving a wide range of reaction conditions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5746. doi:1538-7445.AM2012-5746