The stability of 2-[18F]fluoro-deoxy-D-glucose towards epimerisation under alkaline conditions

Alkaline hydrolysis of 1,3,4,6-tetraacetyl-2-[18F]fluoro-deoxy-D-glucose in the course of 2-[18F]fluoro-deoxy-D-glucose (18FDG) synthesis offers special advantages over acidic hydrolytic procedures, because the reaction time is short and thermal requirements are very mild. In view of the possible epimerization of 2-[18F]fluoro-deoxy-D-glucose a multi-centre study has been performed to check the safety of this method for routine production of 18FDG in view of the quality standards set by the European Pharmacopoeia. The study revealed that in using 0.33 M NaOH for the hydrolysis, a limitation of the reaction temperature to 40°C and a restriction of the reaction time to 5 min represent reaction conditions, which reliably limit the epimerization of 18FDG to 18FDM to 0.5%. Regarding the quality requirements on FDG as set forth by pharmacopoeial standards, alkaline hydrolysis of the intermediate in routine 18FDG production is a safe and efficient reaction pathway, which furthermore obviates the requirement to check for other 2-substituted deoxy-D-glucose derivatives.