Samantha Rossano 1 , 2 , Takuya Toyonaga 1 , Sjoerd J Finnema 1 , Mika Naganawa 1 , Yihuan Lu 1 , Nabeel Nabulsi 1 , Jim Ropchan 1 , Steven De Bruyn 3 , Christian Otoul 3 , Armel Stockis 3 , Jean-Marie Nicolas 3 , Paul Martin 3 , Joel Mercier 3 , Yiyun Huang 1 , R Paul Maguire 3 , Richard E Carson 1 , 2
September 30 2019
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.