Kinetic Analysis of [11C] MP4A Using a High-Radioactivity Brain Region That Represents an Integrated Input Function for Measurement of Cerebral Acetylcholinesterase Activity Without Arterial Blood Sampling

N-[11C]methylpiperidin-4-yl acetate([11C]MP4A) is an acetylcholine analog. It has been used successfully for the quantitative measurement of acetylcholinesterase(AChE) activity in the human brain with positron emission tomography(PET). [11C]MP4A is specifically hydrolyzed by AChE in the brain to a hydrophilic metabolite,which is irreversibly trapped locally in the brain. The authors propose a new method of kinetic analysis of brain AChE activity by PET without arterial blood sampling,that is reference tissue-based ;omear ;east squares(RLS) analysis. In this method, cerebellum or striatum is used as a reference tissue. These regions, because of their high AChE activity, act as a biologic integrator of plasma input function during PET scanning, when regional metabolic rates of [11C] MP4A through AChE(k3,an AChE index) are calculated by using Blomqvist s linear least squares analysis. Computer simulation studies showed that RLS analysis yielded k3 with almost the same accuracy as the standard nonlinear least squares(NLS) analysis in brain regions with low (such as neocortex and hippocampus) and monderately high (thalamus) k3 vallues. The authors then applied these methods to [11C]MP4A PET data in 12 healthy subjects and 26patients with Alzheimer disease(AD) using the cerebellum as the reference region. There was a highly significant linear correlation in regional k3 estimates between RLS and NLS analysis (456 cerebral regions,[RLS k3]=0.98x[NLS ks],gamma=0.92,P<0.001). Significant reductions were observed in k3 estimates of frontal,temporal,parietal,occipital,and sensorimotor cerebral neocortics (P