Review of (18)F-FDG Synthesis and Quality Control

This review article covers a concise account on fludeoxyglucose ((18)F–FDG) synthesis and quality control procedures with emphasis on practical synthesis Currently, (18)F–FDG is the most successful PET radiopharmaceutical so far. The advancement in synthesis and quality control of (18)F–FDG, together with its approval by the US FDA and the availability of reimbursement, are probably the main reasons for the flourish of clinical PET over the last 20 years. (18)F–FDG can be synthesised by either electrophilic fluorination or nucleophilic fluorination reaction. Nucleophilic fluorination using mannose triflate as precursor and Kryptofix or tetrabutylammonium salts (TBA) is widely used because of higher yield and shorter reaction time. The quality control requirements of (18)F–FDG can be found in United States Pharmacopeia (USP), British Pharmacopeia (BP), European Pharmacopeia (EP) and the Chemistry, Manufacturing, and Controls (CMC) section from United States Food and Drug Administration (US FDA) PET draft guidance documents. Basic requirements include radionuclidic identity, radiochemical purity, chemical purity, pH, residual solvent, sterility, and bacterial endotoxin level. Some of these tests (sterility, endotoxins and radionuclidic purity) can be finished after the (18)F–FDG has been released. Although USP, BP and EP do not require filter membrane integrity test, many laboratories perform this test as an indirect evident of the product sterility. It is also interesting to note that there are major differences in (18)F–FDG quality requirements among USP, BP, and CMC.