[¹¹C]HCN Radiochemistry: Recent Progress and Future Perspectives

Abstract

Positron emission tomography (PET) is a unique non-invasive imaging tool for studying in vivo biological processes. It utilizes short-lived positron emitter labeled organic molecules to study biological events in real-time. To incorporate the positron emitter into a molecule of biological interest, radioactive synthons are developed to facilitate radiolabeling chemistry. In addition to 11 C-methylation with [ 11 C]CH 3 I/[ 11 C]CH 3 OTf, 11 Ccarbonylation with [ 11 C]CO, and 11 C-carboxylation of organometallic reagents with [ 11 C]CO 2 , 11 C-cyanation with [ 11 C]HCN is another frequently used 11 C-labeling methodology. It can lead to the generation of [ 11 C]organo-nitriles, [carbonyl-11 C] carboxylic acids, [carbonyl-11 C]aldehydes, [carbonyl-11 C]amides, [ 11 C]alkyl amines, [tetrazoyl-11 C]tetrazoles, [ 11 C]CN-containing heterocycles, etc. This review recognizes the important roles of 11 C-cyanation reactions with the emphasis of recent advances, along with the discussion of molar activities (A m ) of [ 11 C]HCN based radiotracers and prompts for future potential [ 11 C]cyanide based radiotracer development.

Recent Developments in Carbon-11 Chemistry and Applications for First-In-Human PET Studies

“…This is mainly due to its versatility: It can function as nucleophile as well as electrophile, and [ 11 C]cyanide incorporation generates many different functionalities, such as nitriles, hydantoins, (thio)cyanates and, through subsequent reaction, carboxylic acids, aldehydes, amides and amines. Two extensive reviews on [ 11 C]hydrogen cyanide have been recently published, therefore this 11 C-building block will not be discussed in detail herein [ 70 , 71 ]. Since [ 11 C]hydrogen cyanide is one of the few 11 C-building blocks used for FIH PET tracers in recent years (vide infra), we will provide a brief summary of recent work that has not been covered by other reviews.…”

Copper-Mediated Radiocyanation of Unprotected Amino Acids and Peptides

“…We hypothesized that all three of the criteria outlined in Figure could be addressed by developing mild Cu-mediated radiocyanation reactions of aryl halide substrates with [ 11 C]­CN – . Several literature reports have demonstrated the feasibility of such transformations using “ligandless” copper sources (typically either Cu I I or Cu II X/metabisulfite) .…”

Direct C–H Radiocyanation of Arenes via Organic Photoredox Catalysis

“…Carbon-11 ( 11 C, t 1/2 = 20.3 min) is one of the most used positron-emitting isotopes for PET imaging, mainly due to the ubiquitous carbon element in bioactive organic molecules, and the replacement of one of the carbon atoms with an 11 C renders the intrinsic biological properties of the target molecule unchanged for the PET imaging study . In addition, the short half-life of 11 C allows comparisons with other 11 C- or 18 F-labeled tracers in one subject within the same day, minimizing the day-to-day physiological variations during clinical studies and tracer development …”