Quantifying SV2A density and drug occupancy in the human brain using [C-11]UCB-J PET imaging and subcortical white matter as reference tissue
| Autor: | Joël Mercier, Kim Serdons, Brigitte Lacroix, Paul Maguire, David Sciberras, Martijn Devrome, Koen Van Laere, Nathalie Mertens, June van Aalst, Michel Koole |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Positron emission tomography
Synaptic density Occupancy Standardized uptake value Shuttle Radar Topography Mission 030218 nuclear medicine & medical imaging White matter 03 medical and health sciences 0302 clinical medicine Kinetic modelling medicine Radiology Nuclear Medicine and imaging Reference tissue Mathematics medicine.diagnostic_test business.industry Binding potential General Medicine Human brain [11C]UCB-J medicine.anatomical_structure 030220 oncology & carcinogenesis Reference Region Nuclear medicine business |
| Popis: | 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. ispartof: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING vol:46 issue:2 pages:396-406 ispartof: location:Germany status: published |
| Databáze: | OpenAIRE |
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