Pharmacokinetic simulations of spect quantitation of the M 2 muscarinic neuroreceptor subtype in disease states using radioiodinated (R,R)-41QNB

Abstract

Alzheimer's disease (AD) involves selective loss of muscarinic M 2, but not M 1, subtype neuroreceptors in the posterior parietal cortex of the human brain. Emission tomographic study of the loss of M 2 receptors in AD is limited by the fact that there is currently no available M 2-selective radioligand which can penetrate the blood-brain barrier. However, by taking advantage of the different pharmacokinetic properties of (R,R)-[ 123I]IQNB for the M 1 and M 2 subtypes, it may be possible to estimate losses in M 2. It has previously been hypothesized that the difference between an early study and a late study should provide information on the M 2 receptor population. In order to test this hypothesis, we present here the results of pharmacokinetic simulations of the in vivo localization of (R,R)-[ 123I]IQNB in brain regions containing various proportions of M 1 and M 2 subtypes. These results permit us to conclude that SPECT imaging of (R,R)-[ 123I]IQNB localization can potentially be used to quantitate changes in the M 2 subtype in a disease state within a brain region for which the ratio M 2/M 1 is sufficiently high in normal individuals.