Transition‐metal mediated carbonylation with 11C‐labelled carbon monoxide ([11C]CO) is a versatile method for introducing 11C (t1/2 = 20.3 min) into drugs and radioligands for subsequent use in positron emission tomography (PET). The aim of the current study was to perform the 11C‐carbonylation reaction on the interior surface of a stainless‐steel loop used for high performance liquid chromatography (HPLC). In the experimental setup, cyclotron produced 11C‐labelled carbon dioxide ([11C]CO2) was converted to [11C]CO by reduction over heated Molybdenum and swept into an HPLC loop pre‐charged with the appropriate reaction mixture. Following a 5 min reaction, the radiochemical purity (RCP) and the trapping efficiency (TE) of the reaction mixture was determined. After optimization, [11C]N‐Benzylbenzamide was obtained in quantitative radiochemical yield (RCY) following a 5 min reaction at room temperature. The methodology was further applied to label [11C]benzoic acid (RCP≥99%, TE>91%), [11C]methyl benzoate (RCP≥99%, TE>93%) and [11C]phthalide (RCP≥99%, TE>88%). A set of pharmaceuticals was finally radiolabelled using non‐optimized conditions. Excellent yields were obtained for the histamine‐3 receptor radioligand [11C]AZ13198083, the oncology drug [11C]olaparib and the dopamine D2 receptor radioligand [11C]raclopride, whereas a moderate yield was observed for the high‐affinity dopamine D2 receptor radioligand [11C]FLB457. The presented “in‐loop” process proved efficient for diverse 11C‐carbonylations, providing [11C]amides, [11C]esters and [11C]carboxylic acids in moderate to excellent RCYs. Based on the advantages associated with performing the radiolabelling step as an integrated part of the purification system, this methodology may become a valuable addition to the toolbox of methodologies used for 11C‐carbonylation of drugs and radioligands for PET.
carbon monoxide ([ 11 C]CO) is a versatile synthon for radiolabeling of drug-like molecules for imaging studies with positron emission tomography (PET). We here report the development of a novel, user-friendly, fully automated, and good manufacturing practice (GMP) compliant low-pressure synthesis module for 11 C-carbonylation reactions using [ 11 C]CO. In this synthesis module, [ 11 C]CO was reliably prepared from cyclotron-produced [ 11 C]carbon dioxide ([ 11 C]CO 2) by reduction over heated molybdenum and delivered to the reaction vessel within 7 min after end of bombardment, with an overall radiochemical yield (RCY) of 71%. [ 11 C]AZ13198083, a histamine type-3 receptor ligand, was used as a model compound to assess the functionality of the radiochemistry module. At full batch production conditions (55 μA, 30 min), our newly developed low-pressure 11 C-carbonylation apparatus enabled us to prepare [ 11 C]AZ13198083 in an isolated radioactivity of 8540 ± 1400 MBq (n = 3). The radiochemical purity of each of the final formulated batches exceeded 99%, and all other quality control tests results conformed with specifications typically set for carbon-11 labeled radiopharmaceuticals. In conclusion, this novel radiochemistry system offers a convenient GMP compliant production drugs and radioligands for imaging studies in human subjects.
Peatlands are increasingly used as terrestrial archives of atmospheric dust deposition. Peat records mostly cover the Holocene, although some may extend beyond 10 ka (e.g. Kylander et al. 2007). the global occurrence of peatlands makes them a good alternative for making inter-hemispheric comparisons of paleoclimate when other terrestrial records are not available. Europe, for example, lacks long Holocene atmospheric archives such as ice cores, but it contains widespread peat deposits. Similarly, in the Southern Hemisphere, peatlands provide an opportunity to probe the entire Holocene, a period for which dust records from polar ice and marine cores are generally absent or offer lower resolution.
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