Production of 14 Clinical Carbon-11 Radiopharmaceuticals for Neuroimaging Using a GE FASTLab 2 Cassette-Based Synthesis Module

The consistent, on-demand production of carbon-11 radiopharmaceuticals is critical for continued research using positron emission tomography (PET) imaging. Currently, radiopharmaceuticals for PET are typically synthesized using fixed-tube synthesis modules (e.g., GE TRACERLab) requiring extensive cleaning, custom module configurations, and extensive day-of-synthesis setup. Synthesis of radiopharmaceuticals using a cassette-based module (e.g., GE FASTLab) offers a possible solution for complexities associated with fixed-tube modules and increased production consistency, but many imaging agents are labeled with carbon-11 and there are limited reports of cassette-based radiochemistry with this radionuclide. To address this gap, 14 11C-labeled radiopharmaceuticals with applications in functional PET imaging currently synthesized on TRACERLab were translated to the FASTLab using a variety of radiochemistry approaches (resin-based, reactor-based, and loop-based labeling) and various carbon-11 synthons ([11C]CH3I, [11C]CH3OTf, [11C]CO2, [11C]CO, and [11C]HCN). To demonstrate feasibility for routine radiopharmaceutical production, a selection of common radiopharmaceuticals with application in PET imaging ([11C]choline, [11C]PE2i, [11C]carfentanil, [11C]methionine, [11C]sarcosine, [11C]raclopride, [11C]dihydrotetrabenazine, [11C]flumazenil, [11C]butyrate, [11C]butanol, [11C]acetate, [11C]acetylacetate, [1-11C]glycine, and [11C]Pittsburgh compound B) were translated to the FASTLab platform. Radiochemical yields ranged from 2.8 to 38%, radiochemical purities were >90%, and molar activity ranged from 1800 to 14,400 Ci/mmol. These yields and radiochemical purities were comparable to those of previously reported TRACERLab syntheses, demonstrating the versatility of this new cassette-based approach. Additionally, a novel solid phase extraction purification of [11C]raclopride was developed to streamline translation to cassette-based systems. Although further validation studies are required prior to routine use for clinical production, this initial proof of concept demonstrates general compatibility of the FASTLab with carbon-11, opens up 11C radiochemistry to smaller sites that only have cassette-based synthesis modules, and future-proofs the production of 11C-labeled radiopharmaceuticals for PET imaging.