Validation and test-retest repeatability performance of parametric methods for [¹¹C]UCB-J PET

[¹¹C]UCB-J is a PET radioligand that binds to the presynaptic vesicle glycoprotein 2A. Therefore, [¹¹C]UCB-J PET may serve as an in vivo marker of synaptic integrity. The main objective of this study was to evaluate the quantitative accuracy and the 28-day test-retest repeatability (TRT) of various parametric quantitative methods for dynamic [¹¹C]UCB-J studies in Alzheimer's disease (AD) patients and healthy controls (HC). Eight HCs and seven AD patients underwent two 60-min dynamic [¹¹C]UCB-J PET scans with arterial sampling over a 28-day interval. Several plasma-input based and reference-region based parametric methods were used to generate parametric images using metabolite corrected plasma activity as input function or white matter semi-ovale as reference region. Different parametric outcomes were compared regionally with corresponding non-linear regression (NLR) estimates. Furthermore, the 28-day TRT was assessed for all parametric methods. Spectral analysis (SA) and Logan graphical analysis showed high correlations with NLR estimates. Receptor parametric mapping (RPM) and simplified reference tissue model 2 (SRTM2) BP_ND, and reference Logan (RLogan) distribution volume ratio (DVR) regional estimates correlated well with plasma-input derived DVR and SRTM BP_ND. Among the multilinear reference tissue model (MRTM) methods, MRTM1 had the best correspondence with DVR and SRTM BP_ND. Among the parametric methods evaluated, spectral analysis (SA) and SRTM2 were the best plasma-input and reference tissue methods, respectively, to obtain quantitatively accurate and repeatable parametric images for dynamic [¹¹C]UCB-J PET.