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

Abstract

An in-loop ¹¹C-carbonylation process for the radiosynthesis of ¹¹C-carboxylic acids and esters from halide precursors has been developed. The reaction proceeds at room temperature under mild conditions and enables ¹¹C-carbonylation of both electron deficient and electron rich (hetero)aromatic halides to provide ¹¹C-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 [¹¹C]bexarotene and [¹¹C]acetoacetic acid.