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A Postmortem Study to Compare Agonist and Antagonist 5-HT1A Receptor-binding Sites in Alzheimer's Disease.

Becker G, Streichenberger N, Billard T, Newman-Tancredi A, Zimmer L.
CNS Neurosci Ther. 2014 Jul 9. doi: 10.1111/cns.12306. [Epub ahead of print]


AIMS:Positron emission tomography (PET) imaging using 5-HT1A receptor radioligands shows a decreased expression of this serotonin receptor in the hippocampus of patients with Alzheimer's disease (AD) at advanced stages. However, previous 5-HT1A receptor radioligands used in human imaging were antagonists, thought to bind to 5-HT1A receptors in different functional states (i.e., both the one which displays high affinity for agonists and is thought to mediate receptor activation, as well as the functional state which has low affinity for agonists). Comparing the PET imaging obtained using an agonist radioligand, which binds selectively to the functional state of the receptors, with the PET imaging obtained using an antagonist radioligand would therefore provide original information on 5-HT1A receptor impairment during AD.

METHODS: Quantitative autoradiography using [18F]-F15599 and [18F]-MPPF, a 5-HT1A agonist and antagonist, respectively, was measured in hippocampi of 18 patients with AD.

RESULTS: Functional 5-HT1A receptors, labeled by [18F]-F15599, represented ~35% of total receptors, as estimated by 18 F-MPPF labeling. [18F]-F15599 binding decreased in dentate gyrus of patients with AD, as indicated by Braak's stages. In contrast, binding of [18F]-MPPF was statistically unchanged.

CONCLUSION: These in vitro results support testing the concept of functional PET imaging using agonist radioligands in clinical studies.