Enabling Efficient Positron Emission Tomography (PET) Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) with a Robust and One-Step Radiosynthesis of a Highly Potent 18 F-Labeled Ligand ([ 18 F]UCB-H).

Autor: Warnier C; GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium., Lemaire C; GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium., Becker G; GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium., Zaragoza G; Unidad de RX, Universidade de Santiago de Compostela , 15782 Santiago de Compostela, Spain., Giacomelli F; GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium., Aerts J; GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium.; INSERM U1148 , 75018 Paris, France., Otabashi M; Trasis SA , 4430 Ans, Belgium., Bahri MA; GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium., Mercier J; UCB Pharma , 1420 Braine-l'Alleud, Belgium., Plenevaux A; GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium., Luxen A; GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2016 Oct 13; Vol. 59 (19), pp. 8955-8966. Date of Electronic Publication: 2016 Sep 20.
DOI: 10.1021/acs.jmedchem.6b00905
Abstrakt: We herein describe the straightforward synthesis of a stable pyridyl(4-methoxyphenyl)iodonium salt and its [ 18 F] radiolabeling within a one-step, fully automated and cGMP compliant radiosynthesis of [ 18 F]UCB-H ([ 18 F]7), a PET tracer for the imaging of synaptic vesicle glycoprotein 2A (SV2A). Over the course of 1 year, 50 automated productions provided 34 ± 2% of injectable [ 18 F]7 from up to 285 GBq (7.7 Ci) of [ 18 F]fluoride in 50 min (uncorrected radiochemical yield, specific activity of 815 ± 185 GBq/μmol). The successful implementation of our synthetic strategy within routine, high-activity, and cGMP productions attests to its practicality and reliability for the production of large doses of [ 18 F]7. In addition to enabling efficient and cost-effective clinical research on a range of neurological pathologies through the imaging of SV2A, this work further demonstrates the real value of iodonium salts for the cGMP 18 F-PET tracer manufacturing industry, and their ability to fulfill practical and regulatory requirements in that field.
Databáze: MEDLINE