Telescoping the synthesis of the [18F]CABS13 Alzheimer's disease radiopharmaceutical via flow microfluidic rhenium(I) complexations

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John Wiley & Sons, Inc
The syntheses of rhenium(I) complexes were achieved under flow microfluidic conditions. The use of a single microreactor was applied towards complexation of the 6-chloro-2,2'-bipyridine diimine ligand, with ideal complexation conditions around 170 °C. Subsequent radiolabelling with [18F]fluoride was further achieved by flowing through a second heated microreactor, alongside a stream of dried radiofluorination media. Temperature modulation across both microreactors resulted in 23.6 % and 37.0 % radiochemical yield (RCY) of [18F]6-fluoro-2,2'-bipyridine and its associated [18F]tricarbonyl(2-fluoro-2,2'-bipyridine)rhenium(I) chloride complex, respectively. Translation of this set-up to the synthesis of the [18F]CABS13 Alzheimer's disease positron emission tomography (PET) imaging agent was achieved with the incorporation of a third microreactor to enable thermal control of the complexation, fluorination and decomplexation pathways. Optimal RCYs of 2.7 % and 1.9 % of [18F]CABS13 and its rhenium(I) complexation were achieved in-flow, respectively. However, discrepancies in the RCYs were found to arise from differences in the grade of anhydrous dimethyl sulfoxide (DMSO) employed in the continuous-flow reactions. Anhydrous DMSO from Sigma-Aldrich (≤ 99.9 %) in former experiments afforded higher yielders in comparison to replicate experiments employing anhydrous DMSO from Merck Millipore (≤ 99.7 %), thus demonstrating that control of the solvent grade is key to optimizing reaction RCYs. © 2020 Wiley-VCH GmbH
Nervous system diseases, Fluorine 18, Fluorides, Rhenium, Synthesis, Radiopharmaceuticals
Klenner, M. A., Fraser, B. H., Moon, V., Evans, B. J., Massi, M., & Pascali, G. (2020). Telescoping the synthesis of the [18F] CABS13 Alzheimer's disease radiopharmaceutical via flow microfluidic rhenium (I) complexations. European Journal of Inorganic Chemistry, 2020(37), 3554-3564. doi:10.1002/ejic.202000433