Abstract
BackgroundPrevious studies found that the positron emission tomography (PET) radioligand [18F]LSN3316612 accurately quantified O-GlcNAcase in human brain using a two-tissue compartment model (2TCM). This study sought to assess kinetic model(s) as an alternative to 2TCM for quantifying [18F]LSN3316612 binding, particularly in order to generate good-quality parametric images.MethodsThe current study reanalyzed data from a previous study of 10 healthy volunteers who underwent both test and retest PET scans with [18F]LSN3316612. Kinetic analysis was performed at the region level with 2TCM using 120-min PET data and arterial input function, which was considered as the gold standard. Quantification was then obtained at both the region and voxel levels using Logan plot, Ichise's multilinear analysis-1 (MA1), standard spectral analysis (SA), and impulse response function at 120 min (IRF120). To avoid arterial sampling, a noninvasive relative quantification (standardized uptake value ratio (SUVR)) was also tested using the corpus callosum as a pseudo-reference region. Venous samples were also assessed to see whether they could substitute for arterial ones.ResultsLogan and MA1 generated parametric images of good visual quality and their total distribution volume (VT) values at both the region and voxel levels were strongly correlated with 2TCM-derived VT (r = 0.96–0.99) and showed little bias (up to − 8%). SA was more weakly correlated to 2TCM-derived VT (r = 0.93–0.98) and was more biased (~ 16%). IRF120 showed a strong correlation with 2TCM-derived VT (r = 0.96) but generated noisier parametric images. All techniques were comparable to 2TCM in terms of test–retest variability and reliability except IRF120, which gave significantly worse results. Noninvasive SUVR values were not correlated with 2TCM-derived VT, and arteriovenous equilibrium was never reached.ConclusionsCompared to SA and IRF, Logan and MA1 are more suitable alternatives to 2TCM for quantifying [18F]LSN3316612 and generating good-quality parametric images.
Highlights
Neurofibrillary tangles—aggregates of hyperphosphorylated tau protein—are a typical feature of Alzheimer’s disease (AD) and other tauopathies [1]
Lee et al EJNMMI Res (2021) 11:35 hydrolase (O-GlcNAcase, O-GlcNAc hydrolase (OGA)), which catalyze the attachment and detachment of O-GlcNAc, respectively. Because this process modifies the key protein involved in tauopathies, and because OGA is located on chromosome 10q24.1
The whole-brain Total distribution volume (VT) obtained with Loganvoi, MA1voi, and IRF120voi were strongly correlated with VT obtained with Two-tissue compartment model (2TCM) (r > 0.95, P < 0.001 for all) (Table 1). SAvoi showed a significant but slightly weaker correlation (r = 0.90, P < 0.001)
Summary
Neurofibrillary tangles—aggregates of hyperphosphorylated tau protein—are a typical feature of Alzheimer’s disease (AD) and other tauopathies [1]. The process of O-GlcNAcylation [2] involves attaching O-linked β-Nacetylglucosamine (O-GlcNAc) at the serine and threonine residue of tau protein [3]. Two enzymes modulate this process: O-GlcNAc transferase and O-GlcNAc. Lee et al EJNMMI Res (2021) 11:35 hydrolase (O-GlcNAcase, OGA), which catalyze the attachment and detachment of O-GlcNAc, respectively. Lee et al EJNMMI Res (2021) 11:35 hydrolase (O-GlcNAcase, OGA), which catalyze the attachment and detachment of O-GlcNAc, respectively Because this process modifies the key protein involved in tauopathies, and because OGA is located on chromosome 10q24.1 This study sought to assess kinetic model(s) as an alternative to 2TCM for quantifying [18F]LSN3316612 binding, in order to generate good-quality parametric images
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