title: Evaluation of 18F-UCB-H as a novel PET tracer for synaptic vesicle protein 2A in the brain.
abstract: Synaptic vesicle protein 2 isoforms are critical for proper nervous system function and are involved in vesicle trafficking. The synaptic vesicle protein 2A (SV2A) isoform has been identified as the binding site of the antiepileptic levetiracetam (LEV), making it an interesting therapeutic target for epilepsy. (18)F-UCB-H is a novel PET imaging agent with a nanomolar affinity for human SV2A.
  
  
  METHODS
  Preclinical PET studies were performed with isoflurane-anesthetized rats. The arterial input function was measured with an arteriovenous shunt and a β-microprobe system. (18)F-UCB-H was injected intravenously (bolus of 140 ± 20 MBq).
  
  
  RESULTS
  Brain uptake of (18)F-UCB-H was high, matching the expected homogeneous distribution of SV2A. The distribution volume (Vt) for (18)F-UCB-H was calculated with Logan graphic analysis, and the effect of LEV pretreatment on Vt was measured. In control animals the whole-brain Vt was 9.76 ± 0.52 mL/cm(3) (mean ± SD; n = 4; test-retest), and the reproducibility in test-retest studies was 10.4% ± 6.5% (mean ± SD). The uptake of (18)F-UCB-H was dose dependently blocked by pretreatment with LEV (0.1-100 mg/kg intravenously).
  
  
  CONCLUSIONS
  Our results indicated that (18)F-UCB-H is a suitable radiotracer for the imaging of SV2A in vivo. To our knowledge, this is the first PET tracer for the in vivo quantification of SV2A. The necessary steps for the implementation of (18)F-UCB-H production under good manufacturing practice conditions and the first human studies are being planned.
authors.affiliation: Cyclotron Research Centre, University of Liège, Liège, Belgium; and.
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: Warnock
authors.affiliation: Cyclotron Research Centre, University of Liège, Liège, Belgium; and.
authors.forename: Joël
authors.initials: J
authors.lastname: Aerts
authors.affiliation: Cyclotron Research Centre, University of Liège, Liège, Belgium; and.
authors.forename: Mohamed Ali
authors.initials: MA
authors.lastname: Bahri
authors.affiliation: Cyclotron Research Centre, University of Liège, Liège, Belgium; and.
authors.forename: Florian
authors.initials: F
authors.lastname: Bretin
authors.affiliation: Cyclotron Research Centre, University of Liège, Liège, Belgium; and.
authors.forename: Christian
authors.initials: C
authors.lastname: Lemaire
authors.affiliation: Cyclotron Research Centre, University of Liège, Liège, Belgium; and.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Giacomelli
authors.affiliation: Cyclotron Research Centre, University of Liège, Liège, Belgium; and.
authors.forename: Frederic
authors.initials: F
authors.lastname: Mievis
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mestdagh
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Buchanan
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Valade
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: Joël
authors.initials: J
authors.lastname: Mercier
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: Martyn
authors.initials: M
authors.lastname: Wood
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Gillard
authors.affiliation: Cyclotron Research Centre, University of Liège, Liège, Belgium; and.
authors.forename: Alain
authors.initials: A
authors.lastname: Seret
authors.affiliation: Cyclotron Research Centre, University of Liège, Liège, Belgium; and.
authors.forename: André
authors.initials: A
authors.lastname: Luxen
authors.affiliation: Cyclotron Research Centre, University of Liège, Liège, Belgium; and.
authors.forename: Eric
authors.initials: E
authors.lastname: Salmon
authors.affiliation: Cyclotron Research Centre, University of Liège, Liège, Belgium; and Alain.Plenevaux@ulg.ac.be.
authors.forename: Alain
authors.initials: A
authors.lastname: Plenevaux
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011725:Pyridines; D011760:Pyrrolidinones; D011849:Radioactive Tracers; D051381:Rats
chemical_list: D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011725:Pyridines; D011760:Pyrrolidinones; D011849:Radioactive Tracers; C489618:Sv2a protein, rat; C000599325:UCB-H compound; C076414:SV2A protein, human
keywords: 18F; SV2A; brain imaging; microPET