[
11
C]Carbon dioxide ([
11
C]CO
2
) and [
11
C]carbon monoxide ([
11
C]CO) are 2 attractive precursors for labelling the carbonyl position (C═O) in a vast range of functionalised molecules (eg, ureas, amides, and carboxylic acids). The development of radiosynthetic methods to produce functionalised
11
C‐labelled compounds is required to enhance the radiotracers available for positron emission tomography, molecular, and medical imaging applications. Following a brief summary of secondary
11
C‐precursor production and uses, the review focuses on recent progress with direct
11
C‐carboxylation routes with [
11
C]CO
2
and
11
C‐carbonylation with [
11
C]CO. Novel approaches to generate [
11
C]CO using CO‐releasing molecules (CO‐RMs), such as silacarboxylic acids and disilanes, applied to radiochemistry are described and compared with standard [
11
C]CO production methods. These innovative [
11
C]CO synthesis strategies represent efficient and reliable [
11
C]CO production processes, enabling the widespread use of [
11
C]CO chemistry within the wider radiochemistry community.
[11C]Carbon monoxide is an appealing synthon for introducing carbon-11 at a carbonyl position (C=O) in a wide variety of chemotypes (e.g., amides, ketones, acids, esters, and ureas). The prevalence of the carbonyl group in drug molecules and the present-day broad versatility of carbonylation reactions have led to an upsurge in the production of this synthon and in its application to PET radiotracer development. This review focuses on the major advances of the past 15 years.
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