New methodologies for the preparation of carbon-11 labeled radiopharmaceuticals

This short review aims to cover the more recent and promising developments of carbon-11 (¹¹C) labeling radiochemistry and its utility in the production of novel radiopharmaceuticals, with special emphasis on methods that have the greatest potential to be translated for clinical positron emission tomography (PET) imaging.

A survey of the literature was undertaken to identify articles focusing on methodological development in ¹¹C chemistry and their use within novel radiopharmaceutical preparation. However, since ¹¹C-labeling chemistry is such a narrow field of research, no systematic literature search was therefore feasible. The survey was further restricted to a specific timeframe (2000-2016) and articles in English.

From the literature, it is clear that the majority of ¹¹C-labeled radiopharmaceuticals prepared for clinical PET studies have been radiolabeled using the standard heteroatom methylation reaction. However, a number of methodologies have been developed in recent years, both from a technical and chemical point of view. Amongst these, two protocols may have the greatest potential to be widely adapted for the preparation of ¹¹C-radiopharmaceuticals in a clinical setting. First, a novel method for the direct formation of ¹¹C-labeled carbonyl groups, where organic bases are utilized as [¹¹C]carbon dioxide-fixation agents. The second method of clinical importance is a low-pressure ¹¹C-carbonylation technique that utilizes solvable xenon gas to effectively transfer and react [¹¹C]carbon monoxide in a sealed reaction vessel. Both methods appear to be general and provide simple paths to ¹¹C-labeled products.

Radiochemistry is the foundation of PET imaging which relies on the administration of a radiopharmaceutical. The demand for new radiopharmaceuticals for clinical PET imaging is increasing, and ¹¹C-radiopharmaceuticals are especially important within clinical research and drug development. This review gives a comprehensive overview of the most noteworthy ¹¹C-labeling methods with clinical relevance to the field of PET radiochemistry.