Assessment of muscarinic receptor concentrations in affinity and Alzheimerdisease with [C-11]NMPB and PET

Cerebral cholinergic deficits have been described in Alzheimer disease (AD) and as a result of normal aging. At the present time, there are very limit ed options for the quantification of cholinergic receptors with in vivo ima ging techniques such as PET. In the present study, we examined the feasibil ity of utilizing [C-11]N-methyl-4-piperidyl benzilate (NMPB), a nonselectiv e muscarinic receptor ligand, in the study of aging and neurodegenerative p rocesses associated with cholinergic dysfunction. Based on prior data descr ibing the accuracy of various kinetic methods, we examined the concentratio n of muscarinic receptors with [C-11]NMPB and PET using two- and three-comp artment; kinetic models. Eighteen healthy subjects and six patients diagnos ed with probable AD were studied. Pixel-by-pixel two-compartment model fits showed acceptable precision in the study of normal aging, with comparable results to those obtained with a more complex and less precise three-compar tment model. Normal aging was associated with a reduction in muscarinic rec eptor binding in neocortical regions and thalamus. In AD patients, the thre e-compartment model appeared capable of dissociating changes in tracer tran sport from changes in receptor binding, but suffered from statistical uncer tainty, requiring normalization to a reference region, and therefore limiti ng its potential use in the study of neurodegenerative processes. After nor malization, no regional changes in muscarinic receptor concentrations were observed in AD. Synapse 39:275-287, 2001, (C) 2001 Wiley-Liss, Inc.