Reliable set-up for in-loop 11C-carboxylations using Grignard reactions for the preparation of [carbonyl-11C]WAY-100635 and [11C]-(+)-PHNO

Abstract

Aim of this work was the implementation of a generalized in-loop synthesis for 11C-carboxylations and subsequent 11C-acylations on the TRACERlab FxC Pro platform. The set-up was tested using [carbonyl-11C]WAY-100635 and, for the first time, [11C]-(+)-PHNO. Its general applicability could be demonstrated and both [carbonyl-11C]WAY-100635 and [11C]-(+)-PHNO were prepared with high reliability and satisfying outcome.

Recent Progress in Metal Catalyzed Direct Carboxylation of Aryl Halides and Pseudo Halides Employing CO2: Opportunities for 11C Radiochemistry

“…It has been reported as one of the primary sources of non‐radioactive CO 2 to cause a decrease in the SA of carbon‐11 labelled products . Furthermore, low (around 20 GBq μmol −1 ) or highly varying SAs have been observed for radiotracers obtained by Grignard based C ‐ and N ‐ 11 C‐carboxylations . The reaction methodology described here mostly proceed by CO 2 insertion on Ar‐M‐L (aryl‐metal–ligand) intermediates and there is little chance that atmospheric CO 2 could contaminate pre‐activated precursors (Grignard reagents and ArLi compounds) as the Ar‐M‐L intermediates are only formed in situ in the final reactor.…”

Interaction between 5-HTTLPR and 5-HT1B genotype status enhances cerebral 5-HT1A receptor binding

“…Subjects were instructed not to move and to speak only in case of emergency, while a polyurethane cushion and head straps were used to minimize head movement, guaranteeing a soft head rest during the whole scanning period. For a complete description of the synthesis of [carbonyl-11 C]WAY-100635 please see Rami-Mark et al (2013) and Wadsak et al (2007). Mean injected dose of the radioligand was 293.08 ± 92.11 MBq, specific radioactivity at time of injection was 285.5 ± 251.2 GBq/μmol and radiochemical purity was above 95%.…”

In‐loop flow [11C]CO2 fixation and radiosynthesis of N,N′‐[11C]dibenzylurea

“…Carbon-11 is produced as [ 11 C]CO 2 (primary precursor), by the cyclotron proton-bombardment of nitrogen-14 via the 14 N(p,α) 11 C nuclear reaction. The relatively low reactivity and solubility of [ 11 C]CO 2 leads to its rapid conversion to more reactive secondary precursors.…”

“…The relatively low reactivity and solubility of [ 11 C]CO 2 leads to its rapid conversion to more reactive secondary precursors. 1 The most prevalent of these secondary precursors is [ 11 C] CH 3 I for 11 C-methylation reactions. 1 While these reactions are used to produce the vast majority of carbon-11 radiotracers, in the time taken to convert [ 11 C]CO 2 to [ 11 C]CH 3 I, significant amounts of the starting radioactivity can be lost through multistep synthesis and radioactive decay.…”

“…6 In addition, 11 C-methylation can somewhat limit the chemical space available for radiolabelling. As such, there have been a variety of alternative secondary and tertiary 11 C-precursors developed to convert the poorly reactive [ 11 C]CO 2 into a more versatile toolbox for the 11 Cradiochemist: [ 11 C]CO, [ 11 C]HCN, [ 11 C]CS 2 , [ 11 C] CH 3 OTf, and [ 11 C]COCl 2 are just a few examples. 1 In an effort to avoid this time-consuming conversion to more reactive precursors, [ 11 C]CO 2 has been reacted directly with Grignard reagents (alkyl magnesium bromide) to synthesise 11 C-carboxylic acid derivatives such as [ 11 C] acetate, [ 11 C]palmitic acid, and 2-[ 11 C]octynoic acid.…”