Development of a fully automated low-pressure [11C]CO carbonylation apparatus

[C-11]carbon monoxide ([C-11]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 [C-11]CO. In this synthesis module, [C-11]CO was reliably prepared from cyclotron-produced [C-11]carbon dioxide ([C-11]CO2) 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%. [C-11]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 mu A, 30 min), our newly developed low-pressure(11)C-carbonylation apparatus enabled us to prepare [C-11]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.