Improved synthesis and application of [11C]benzyl iodide in positron emission tomography radiotracer production

Positron emission tomography has increased the demand for new carbon‐11 radiolabeled tracers and building blocks. A promising radiolabeling synthon is ¹¹C]benzyl iodide (¹¹C]BnI), because the benzyl group is a widely present functionality in biologically active compounds. Unfortunately, synthesis of ¹¹C]BnI has received little attention, resulting in limited application. Therefore, we investigated the synthesis in order to significantly improve, automate, and apply it for labeling of the dopamine D₂ antagonist ¹¹C]clebopride as a proof of concept. ¹¹C]BnI was synthesized from ¹¹C]CO₂ via a Grignard reaction and purified prior the reaction with desbenzyl clebopride. According to a one‐pot procedure, ¹¹C]BnI was synthesized in 11 min from ¹¹C]CO₂ with high yield, purity, and specific activity, 52 ± 3% (end of the cyclotron bombardment), 95 ± 3%, and 123 ± 17 GBq/µmol (end of the synthesis), respectively. Changes in the ¹¹C]BnI synthesis are reduced amounts of reagents, a lower temperature in the Grignard reaction, and the introduction of a solid‐phase intermediate purification. ¹¹C]Clebopride was synthesized within 28 min from ¹¹C]CO₂ in an isolated decay‐corrected yield of 11 ± 3% (end of the cyclotron bombardment) with a purity of >98% and specific activity (SA) of 54 ± 4 GBq/µmol (n = 3) at the end of the synthesis. Conversion of ¹¹C]BnI to product was 82 ± 11%. The reliable synthesis of ¹¹C]BnI allows the broad application of this synthon in positron emission tomography radiopharmaceutical development. Copyright © 2015 John Wiley & Sons, Ltd.