Quantifying SV2A density and drug occupancy in the human brain using [11C]UCB-J PET imaging and subcortical white matter as reference tissue
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Purpose A [11 C]UCB-J blocking study was performed in healthy volunteers to validate simplified, non-invasive measures for quantifying presynaptic SV2A expression using subcortical white matter as reference tissue.Methods Ninety minutes dynamic [11 C]UCB-J PET scanning with arterial blood sampling was performed in 10 healthy volunteers (8 M/2F; age 27.6 ± 10.0 yrs), before and after administration of a novel chemical entity with selective affinity for SV2A. The centrum semi-ovale (SO) was validated as reference region by comparing baseline and post treatment distribution volume (V T). Using SO as reference tissue, Binding Potential (BP SO) using a Simplified Reference Tissue Model (SRTM, down to 60 min acquisition) and Standardized Uptake Value Ratios (60-90 min post injection - SUVR SO,60-90min) were compared with regional distribution volume ratios (DVR). Next, SV2A occupancy values based on SRTM BP SO and SUVR SO,60-90min were compared to occupancy estimates using regional V T values and a Lassen plot.Results After pretreatment, regional V T values were reduced significantly except for SO. Highly significant correlations were found between DVR, SRTM BP SO and SUVR SO,60-90min. Compared to DVR, baseline SRTM BP SO showed a small bias (≤ 6.1%) with lower precision for shorter acquisition times, while SUVR SO,60-90min showed 3.5% bias with similar precision. Differences between SV2A occupancy values based on SUVR SO,60-90min and occupancy estimates using V T and a Lassen plot were small but significant, while negligible bias was found for SRTM based occupancy estimates (at least 70 min acquisition).Conclusion This [11 C]UCB-J blocking study validated SO as a suitable reference region for non-invasive quantification of SV2A availability and drug occupancy in the human brain. Accurate quantification can be achieved by using either SUVR SO,60-90min with a 60-90 min PET acquisition or SRTM BP SO with at least 70 min dynamic PET acquisition.
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The simplified quantification method (SUVR) has been validated in healthy aging and in AD, but not in LLD.
“This quantification method has been validated in healthy aging [33] and in AD [55], but not in LLD.”
From Preliminary evidence for preserved synaptic density in late-life depression (2024) · cites this paper as [33]
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References 25 · Cited by 118
- Authors
- Koole, M., van Aalst, J., Devrome, M., Mertens, N., Serdons, K., Lacroix, B., Mercier, J., Sciberras, D., Maguire, P., & Van Laere, K.
- Affiliations
- KU Leuven (BE)
- UCB Pharma (Belgium) (BE)
- Corresponding author
- Koole, Michel
- Venue
- European Journal of Nuclear Medicine and Molecular Imaging
- Published
- 2018-08-18
- Volume
- 46
- Issue
- 2
- Pages
- 396-406
- ISSN
- 1619-7070 (ISSN-L)
- 1619-7089
- OpenAlex
- W2887203046
- Cited by
- 118
- References
- 25
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 17 · 2023: 14 · 2022: 36 · 2021: 16 · 2020: 15 · 2019: 9
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- green
- lirias.kuleuven.be
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Funders
- KU Leuven
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Keywords
- SV2A, [11C]UCB-J, reference tissue, subcortical white matter, binding potential, simplified reference tissue model, standardized uptake value ratio, distribution volume ratio, human brain, PET quantification
- MeSH terms
- Adult, Female, Gene Expression Regulation, Humans, Kinetics, Magnetic Resonance Imaging, Male, Membrane Glycoproteins, Middle Aged, Models, Biological, Nerve Tissue Proteins, Pyridines, Pyrrolidinones, Reference Standards, Positron-Emission Tomography, Young Adult, Multimodal Imaging, White Matter
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