Open AccessA Postmortem Study to Compare Agonist and Antagonist 5‐ HT 1A Receptor‐binding Sites in Alzheimer's Disease
Author(s) -
Becker Guillaume,
Streichenberger Nathalie,
Billard Thierry,
NewmanTancredi Adrian,
Zimmer Luc
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12306
Subject(s) - radioligand , agonist , receptor , antagonist , radioligand assay , chemistry , 5 ht receptor , medicine , receptor antagonist , dentate gyrus , endocrinology , pharmacology , serotonin , hippocampus , neuroscience , psychology
Summary Aims Positron emission tomography ( PET ) imaging using 5‐ HT 1A 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‐ HT 1A receptor radioligands used in human imaging were antagonists, thought to bind to 5‐ HT 1A 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‐ HT 1A receptor impairment during AD . Methods Quantitative autoradiography using 18 F‐F15599 and 18 F‐ MPPF , a 5‐ HT 1A agonist and antagonist, respectively, was measured in hippocampi of 18 patients with AD . Results Functional 5‐ HT 1A receptors, labeled by 18 F‐F15599, represented ~35% of total receptors, as estimated by 18 F‐ MPPF labeling. 18 F‐F15599 binding decreased in dentate gyrus of patients with AD , as indicated by Braak's stages. In contrast, binding of 18 F‐ MPPF was statistically unchanged. Conclusion These in vitro results support testing the concept of functional PET imaging using agonist radioligands in clinical studies.