Standardization of fluorine-18 manufacturing processes: New scientific challenges for PET

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 78; no. 3; pp. 307 - 313
• Main Authors: Hjelstuen, Ole K., Svadberg, Anders, Olberg, Dag E., Rosser, Mark
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.2011; Elsevier
• Subjects: 18F-chemistry; Animals; Automation; Biological and medical sciences; Drug Compounding - methods; Drug Compounding - standards; Drug Stability; Fluorine Radioisotopes - standards; Fluorodeoxyglucose F18 - chemistry; Fluorodeoxyglucose F18 - standards; General pharmacology; Glass/plastic leachables; Humans; Investigative techniques, diagnostic techniques (general aspects); Isotope Labeling; Manufactured Materials - standards; Medical sciences; Miscellaneous. Technology; PET; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Positron-Emission Tomography - methods; Radionuclide investigations; Reference Standards; Standardization; 18F-chemistry; Automation; Glass/plastic leachables; PET; Standardization; Ethylene terephthalate polymer; Performance evaluation; Pharmaceutical technology; Fluorine; Ester polymer; Exploration; Manufacturing process; Technique; Plastics; Emission tomography
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2011.01.002

In [ 18F]fluoride chemistry, the minute amounts of radioactivity taking part in a typical radiolabeling reaction as in the attached flow-chart are easily outnumbered by other reactants. Surface areas become comparably larger and more influential than in standard fluorine chemistry, while leachables, extractables and other components that normally are considered small impurities can have a considerable influence on the efficiency of the reaction. There are still areas of limited knowledge in the fundamental [ 18F]fluoride chemistry and there is a number of pharmaceutical factors that could influence several steps and the final outcome of the 18F-radiosynthesis. In [ 18F]fluoride chemistry, the minute amounts of radioactivity taking part in a radiolabeling reaction are easily outnumbered by other reactants. Surface areas become comparably larger and more influential than in standard fluorine chemistry, while leachables, extractables, and other components that normally are considered small impurities can have a considerable influence on the efficiency of the reaction. A number of techniques exist to give sufficient 18F-tracer for a study in a pre-clinical or clinical system, but the chemical and pharmaceutical understanding has significant gaps when it comes to scaling up or making the reaction more efficient. Automation and standardization of [ 18F]fluoride PET tracers is a prerequisite for reproducible manufacturing across multiple PET centers. So far, large-scale, multi-site manufacture has been established only for [ 18F]FDG, but several new tracers are emerging. In general terms, this transition from small- to large-scale production has disclosed several scientific challenges that need to be addressed. There are still areas of limited knowledge in the fundamental [ 18F]fluoride chemistry. The role of pharmaceutical factors that could influence the 18F-radiosynthesis and the gaps in precise chemistry knowledge are discussed in this review based on a normal synthesis pattern.