title: Improved synthesis and application of [(11) C]benzyl iodide in positron emission tomography radiotracer production.
abstract: Positron emission tomography has increased the demand for new carbon-11 radiolabeled tracers and building blocks. A promising radiolabeling synthon is [(11) C]benzyl iodide ([(11) C]BnI), because the benzyl group is a widely present functionality in biologically active compounds. Unfortunately, synthesis of [(11) C]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 [(11) C]clebopride as a proof of concept. [(11) C]BnI was synthesized from [(11) C]CO2 via a Grignard reaction and purified prior the reaction with desbenzyl clebopride. According to a one-pot procedure, [(11) C]BnI was synthesized in 11 min from [(11) C]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 [(11) C]BnI synthesis are reduced amounts of reagents, a lower temperature in the Grignard reaction, and the introduction of a solid-phase intermediate purification. [(11) C]Clebopride was synthesized within 28 min from [(11) C]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 [(11) C]BnI to product was 82 ± 11%. The reliable synthesis of [(11) C]BnI allows the broad application of this synthon in positron emission tomography radiopharmaceutical development.
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Pekošak
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Filp
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lonneke
authors.initials: L
authors.lastname: Rotteveel
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Poot
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert D
authors.identifier: http://orcid.org/0000-0002-1250-7656
authors.initials: AD
authors.lastname: Windhorst
mesh_terms: D001593:Benzyl Compounds / Q000138:chemical synthesis*; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes; D006801:Humans; D006847:Hydrocarbons, Iodinated / Q000138:chemical synthesis*; D007553:Isotope Labeling / Q000379:methods; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*
chemical_list: D001593:Benzyl Compounds; D002250:Carbon Radioisotopes; D006847:Hydrocarbons, Iodinated; D019275:Radiopharmaceuticals
keywords: N-alkylation reaction; [11C]benzyl iodide; [11C]clebopride; carbon-11; positron emission tomography; radiolabeling