Enabling Efficient Positron Emission Tomography (PET) Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) with a Robust and One-Step Radiosynthesis of a Highly Potent18F-Labeled Ligand ([18F]UCB-H).
We herein describe the straightforward synthesis of a stable pyridyl(4-methoxyphenyl)iodonium salt and its [18F] radiolabeling within a one-step, fully automated and cGMP compliant radiosynthesis of [18F]UCB-H ([18F]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 [18F]7 from up to 285 GBq (7.7 Ci) of [18F]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 [18F]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 cGMP18F-PET tracer manufacturing industry, and their ability to fulfill practical and regulatory requirements in that field.
GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium.
Corentin
C
Warnier
GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium.
Christian
C
Lemaire
GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium.
Guillaume
G
Becker
Unidad de RX, Universidade de Santiago de Compostela , 15782 Santiago de Compostela, Spain.
Guillermo
G
Zaragoza
GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium.
Fabrice
F
Giacomelli
GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium.|INSERM U1148 , 75018 Paris, France.
Joël
J
Aerts
Trasis SA , 4430 Ans, Belgium.
Muhammad
M
Otabashi
GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium.
Mohamed Ali
MA
Bahri
UCB Pharma , 1420 Braine-l'Alleud, Belgium.
Joël
J
Mercier
GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium.
Alain
A
Plenevaux
GIGA Cyclotron Research Centre In Vivo Imaging, University of Liege , 4000 Liege, Belgium.
André
A
Luxen
D000818:Animals; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000032:analysis*; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005462:Fluorine Radioisotopes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011725:Pyridines; D011760:Pyrrolidinones; C489618:Sv2a protein, rat; C000599325:UCB-H compound