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.