1. Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA;2. Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA;3. Department of Chemistry and Biochemistry, University of California, Santa Barbara, California, USA;4. Department of Neuroscience, Physical Therapy and Occupational Therapy, Washington University School of Medicine, St. Louis, Missouri, USA
Abstract:
Molecular imaging of vesicular acetylcholine transporter (VACh T) in the brain provides an important cholinergic biomarker for the pathophysiology and treatment of dementias including Alzheimer's disease. In this study, kinetics modeling methods were applied and compared for quantifying regional brain uptake of the VACh T‐specific positron emission tomography radiotracer, ((?)‐(1‐(‐8‐(2‐fluoroethoxy)‐3‐hydroxy‐1,2,3,4‐tetrahydronaphthalen‐2‐yl)piperidin‐4‐yl)(4‐fluorophenyl)‐methanone) ([18F]VAT ) in macaques. Total volume distribution (V T ) estimates were compared for one‐tissue compartment model (1TCM ), two‐tissue compartment model (2TCM ), Logan graphic analysis (LoganAIF ) and multiple linear analysis (MA 1) with arterial blood input function using data from three macaques. Using the cerebellum‐hemispheres as the reference region with data from seven macaques, three additional models were compared: reference tissue model (RTM ), simplified RTM (SRTM ), and Logan graphic analysis (LoganREF ). Model selection criterion indicated that a) 2TCM and SRTM were the most appropriate kinetics models for [18F]VAT ; and b) SRTM was strongly correlated with 2TCM (Pearson's coefficients r > 0.93, p < 0.05). Test–retest studies demonstrated that [18F]VAT has good reproducibility and reliability (TRV < 10%, ICC > 0.72). These studies demonstrate [18F]VAT is a promising VACh T positron emission tomography tracer for quantitative assessment of VACh T levels in the brain of living subjects.
