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

[¹¹ C]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]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%. [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.