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      Assessment of a white matter reference region for11C-UCB-J PET quantification

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          Abstract

          11C-UCB-J is a positron emission tomography (PET) radioligand that has been used in humans for synaptic vesicle glycoprotein 2A (SV2A) imaging and as a potential synaptic density marker. The centrum semiovale (CS) is a proposed reference region for noninvasive quantification of 11C-UCB-J, due to negligible concentrations of SV2A in this region in baboon brain assessed by in vitro methods. However, in displacement scans with SV2A-specific drug levetiracetam in humans, a decrease in 11C-UCB-J concentration was observed in the CS, consistent with some degree of specific binding. The current study aims to validate the CS as a reference region by (1) optimizing CS region of interest (ROI) to minimize spill-in from gray matter with high radioactivity concentrations; (2) investigating convergence of CS ROI values using ordered subset expectation maximization (OS-EM) reconstruction, and (3) comparing baseline CS volume of distribution ( V T) to nondisplaceable uptake in gray matter, V ND. Improving ROI definition and increasing OS-EM iterations during reconstruction decreased the difference between CS V Tand V ND. However, even with these corrections, CS V Toverestimated V NDby ∼35–40%. These measures showed significant correlation, suggesting that, though biased, the CS may be a useful estimate of nondisplaceable uptake, allowing for noninvasive quantification for SV2A PET.

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          Author and article information

          Contributors
          (View ORCID Profile)
          (View ORCID Profile)
          Journal
          Journal of Cerebral Blood Flow & Metabolism
          J Cereb Blood Flow Metab
          SAGE Publications
          0271-678X
          1559-7016
          September 2020
          September 30 2019
          September 2020
          : 40
          : 9
          : 1890-1901
          Affiliations
          [1 ]Department of Radiology and Biomedical Imaging, Yale PET Center, Yale School of Medicine, New Haven, CT, USA
          [2 ]Department of Biomedical Engineering, Yale University, New Haven, CT, USA
          [3 ]UCB Pharma, Brussels, Belgium
          Article
          10.1177/0271678X19879230
          © 2020

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