Radiosynthesis of 11C-phenytoin Using a DEGDEE Solvent for Clinical PET Studies

Abstract

Objective(s): Phenytoin is an antiepileptic drug that is used worldwide.The whole-body pharmacokinetics of this drug have been extensivelystudied using 11C-phenytoin in small animals. However, because ofthe limited production amounts that are presently available, clinical11C-phenytoin PET studies to examine the pharmacokinetics of phenytoinin humans have not yet been performed. We aimed to establish a newsynthesis method to produce large amounts of 11C-phenytoin to conducthuman studies.Methods: 11C-methane was produced using an in-house cyclotron by the14N (p, α) 11C nuclear reaction of 5 % of hydrogen containing 95 % ofnitrogen gas. About 30 GBq of 11C-methane was then transferred to ahomogenization cell containing Fe2O3 powder mixed with Fe granulesheated at 320 0C to yield 11C-phosgene. Xylene, 1,4-dioxane, and diethyleneglycol diethyl ether (DEGDEE) were investigated as possible reactionsolvents.Results: The ratio of 11C-phenytoin radioactivity to the total 11C radioactivityin the reaction vessel (reaction efficiency) was 7.5% for xylene, 11% for1,4-dioxane, and 37% for DEGDEE. The synthesis time was within 45 minfrom the end of bombardment until obtaining the final product. Theradioactivity produced was more than 4.1 GBq in 10 mL of saline at the endof synthesis. The specific activity of the product ranged from 1.7 to 2.2GBq/μmol. The quality of the 11C-phenytoin injection passed all criteriarequired for clinical use.Conclusion: The use of DEGDEE as a solvent enabled the production of alarge amount of 11C-phenytoin sufficient to enable PET studies examiningthe human pharmacokinetics of phenytoin.

Keywords

• PET
• Radiosynthesis
• 11C-phenytoin
• Radiopharmacy