title: In vivo muscarinic 2 receptor imaging in cognitively normal young and older volunteers.
abstract: The precise effects of normal aging on the cholinergic system are unknown, as both in vitro and PET studies have shown conflicting results. In vivo determination of muscarinic receptor distribution and density has been hampered by both poor subtype selectivity and/or blood-brain barrier permeability of known ligands. Previous in vitro and in vivo work with the F-18 labeled muscarinic agonist, 3-(3- (3-[(18)F]Flouropropyl)thio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine ((18)FP-TZTP) suggested the use of (18)FP-TZTP to selectively quantify M2 receptors in humans. In this study, we used (18)FP-TZTP to infer M2 receptor avidity in the brains of 15 healthy younger subjects (mean age = 28.3 +/- 5.5 years) and 20 healthy older subjects (mean age = 62.1 +/- 7.7 years). Corrections for subject motion during the 120-min acquisition and partial voluming (PVC) were performed. A one-tissue compartment model was used to estimate the volumes of distribution (V(T)) of (18)FP-TZTP. Within both groups of subjects, volumes of distribution (K(1)/k(2)) in cortical, subcortical, and cerebellar areas were consistent with M2 receptor topography. Compared to younger subjects older subjects had significantly higher means and standard deviations for the volumes of distribution of (18)FP-TZTP throughout much of the cerebellum, cortex, and subcortex (Global Gray V(T) = 742 +/- 163 in older subjects and 645 +/- 74 in younger subjects, P < 0.03). Across all subjects (18)FP-TZTP, regional, and Global Gray distribution volumes were significantly correlated to age (Global Gray V(T,) r = 0.41, P < 0.01). A lower concentration of acetylcholine in the synapse of some older subjects is one possible explanation for the data.
authors.affiliation: Geriatric Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Podruchny
authors.forename: Catherine
authors.initials: C
authors.lastname: Connolly
authors.forename: Arun
authors.initials: A
authors.lastname: Bokde
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: Trey
authors.initials: T
authors.lastname: Sunderland
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cohen
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging; D001921:Brain / Q000000981:diagnostic imaging*; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000493:pharmacokinetics*; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013844:Thiazoles / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods
chemical_list: D005462:Fluorine Radioisotopes; D011725:Pyridines; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D013844:Thiazoles; C115177:FP-TZTP; D000109:Acetylcholine