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 [C-11]benzyl iodide ([C-11]BnI), because the benzyl group is a widely present functionality in biologically active compounds. Unfortunately, synthesis of [C-11]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 D-2 antagonist [C-11]clebopride as a proof of concept. [C-11]BnI was synthesized from [C-11]CO2 via a Grignard reaction and purified prior the reaction with desbenzyl clebopride. According to a one-pot procedure, [C-11]BnI was synthesized in 11min from [C-11]CO2 with high yield, purity, and specific activity, 52 +/- 3% (end of the cyclotron bombardment), 95 +/- 3%, and 123 +/- 17GBq/mu mol (end of the synthesis), respectively. Changes in the [C-11]BnI synthesis are reduced amounts of reagents, a lower temperature in the Grignard reaction, and the introduction of a solid-phase intermediate purification. [C-11]Clebopride was synthesized within 28min from [C-11]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 +/- 4GBq/mu mol (n=3) at the end of the synthesis. Conversion of [C-11]BnI to product was 82 +/- 11%. The reliable synthesis of [C-11]BnI allows the broad application of this synthon in positron emission tomography radiopharmaceutical development. Copyright (c) 2015 John Wiley & Sons, Ltd.