Evaluation of18F-UCB-H as a Novel PET Tracer for Synaptic Vesicle Protein 2A in the Brain
Open accessAbstract
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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Three of the SV2A ligands were radiolabeled as [11C]UCB-A, [18F]UCB-H, and [11C]UCB-J, and all were evaluated in nonhuman primates.
“Three of the SV2A ligands were radiolabeled as [ 11 C] UCB-A [112], [ 18 F]UCB-H [113-116], and [ 11 C]UCB-J [117], and all were evaluated in nonhuman primates (NHP).”
From Challenges and rewards of in vivo synaptic density imaging, and its application to the study of depression (2025) · cites this paper as [113]
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References 29 · Cited by 85
Research works printed but not linked: 2
- 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.
- 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)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society 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
- bronze
- doi.org
- 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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