The objective of this project is to develop and implement techniques for the in vivo assay of muscarinic cholinergic receptors in the central nervous system. This will be performed by the use of an intravenously administered iodinated radiopharmaceutical with very high affinity for the muscarinic receptor in conjunction with quantitative external imaging using Single Photon Emission Computerized Tomography (SPECT). The muscarinic receptor ligand we proposed to use [123I]3-quinuclidinyl-(3-iodo-4-hydroxybenzilate) (I-OH-QNB). This technique will ultimately be used to study muscarinic receptors in patients with Alzheimer's Disease. In a longitudinal fashion, we plan to study the alterations of the relative regional and absolute muscarinic receptor densities in patients with Alzheimer's Disease. This data will be obtained in parallel with careful cognitive and neurologic follow up. Additional correlation with neuropathologic examination of the muscarinic system may in some cases be possible.
