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A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
Quantifying SV2A density and drug occupancy in the human brain using [11C]UCB-J PET imaging and subcortical white
Michel Koole1, June van Aalst2, Martijn Devrome2
1Department of Nuclear Medicine and Molecular Imaging, KU Leuven, Herestraat 49, 3000, Leuven, Belgium. michel.koole@kuleuven.be.
Purpose:
A [11C]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 [11C]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 (VT). Using SO as reference tissue, Binding Potential (BPSO) using a Simplified Reference Tissue Model (SRTM, down to 60 min acquisition) and Standardized Uptake Value Ratios (60-90 min post injection - SUVRSO,60-90min) were compared with regional distribution volume ratios (DVR). Next, SV2A occupancy values based on SRTM BPSO and SUVRSO,60-90min were compared to occupancy estimates using regional VT values and a Lassen plot.
Results:
After pretreatment, regional VT values were reduced significantly except for SO. Highly significant correlations were found between DVR, SRTM BPSO and SUVRSO,60-90min. Compared to DVR, baseline SRTM BPSO showed a small bias (≤ 6.1%) with lower precision for shorter acquisition times, while SUVRSO,60-90min showed 3.5% bias with similar precision. Differences between SV2A occupancy values based on SUVRSO,60-90min and occupancy estimates using VT 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 [11C]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 SUVRSO,60-90min with a 60-90 min PET acquisition or SRTM BPSOwith at least 70 min dynamic PET acquisition.
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