Cited by 85Radiopharmaceutical Chemistry and ApplicationsMedical Imaging Techniques and ApplicationsNeuroscience and Neuropharmacology Research

Evaluation of18F-UCB-H as a Novel PET Tracer for Synaptic Vesicle Protein 2A in the Brain

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Warnock, Geoffrey I., Aerts, Joël, Bahri, Mohamed Ali, Bretin, Florian, Lemaire, Christian, Giacomelli, Fabrice, Mievis, Frederic, Mestdagh, Nathalie +9 more·2014·Journal of Nuclear Medicine

Abstract

UNLABELLED: 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). CONCLUSION: 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.

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References 29 · Cited by 85

Research works printed but not linked: 2

  1. Aerts J, Otabashi M, Giacomelli F, et al. Radiosynthesis and first small animal microPET imaging of [ 18 F]UCB-H, a new fluorine-18 labelled tracer targeting synaptic vesicle protein 2A (SV2A): EANM Abstracts 2013. Eur J Nucl Med Mol Imaging. 2013;40:S89-S565.
  2. Weber B, Späth N, Wyss M, et al. Quantitative cerebral blood flow measurements in the rat using a beta-probe and H2 15O. J Cereb Blood Flow Metab. 2003;23:1455-1460.

Authors
Warnock, G. I., Aerts, J., Bahri, M. A., Bretin, F., Lemaire, C., Giacomelli, F., Mievis, F., Mestdagh, N., Buchanan, T., Valade, A., Mercier, J., Wood, M., Gillard, M., Seret, A., Luxen, A., Salmon, E., & Plenevaux, A.
Affiliations
  • University of Liège (BE)
  • UCB Pharma (Belgium) (BE)
Venue
Journal of Nuclear Medicine
Published
2014-06-16
Volume
55
Issue
8
Pages
1336-1341
ISSN
  • 0161-5505 (ISSN-L)
  • 2159-662X
OpenAlex
W2121123181
Cited by
85
References
29
Citations by year
2026: 7 · 2025: 4 · 2024: 9 · 2023: 4 · 2022: 11 · 2021: 7 · 2020: 12 · 2019: 8 · 2018: 4 · 2017: 11 · 2016: 6 · 2015: 1 · 2014: 1
FWCI
4.93
Type
journal article
Language
en
Open access
Locations
  • Journal of Nuclear Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • ORBi (University of Liège) (submittedVersion)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
SV2A, PET radiotracer, levetiracetam, epilepsy, test-retest reproducibility, arterial input function
MeSH terms
Animals, Brain, Humans, Male, Membrane Glycoproteins, Nerve Tissue Proteins, Pyridines, Pyrrolidinones, Radioactive Tracers, Positron-Emission Tomography, Rats

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