Automated production of ¹¹C-labeled carboxylic acids and esters via "in-loop" ¹¹C-carbonylation using GE FX synthesis modules

An in-loop C-11-carbonylation process for the radiosynthesis of C-11-carboxylic acids and esters from halide precursors has been developed. The reaction proceeds at room temperature under mild conditions and enables C-11-carbonylation of both electron deficient and electron rich (hetero)aromatic halides to provide C-11-carboxylic acids and esters in good to excellent radiochemical yields, high radiochemical purity, and excellent molar activity. The process has been fully automated using commercial radiochemistry synthesis modules, and application to clinical production is demonstrated via validated cGMP radiosyntheses of [C-11]bexarotene and [C-11]acetoacetic acid.