Quantitative autoradiography with short-lived positron emission tomography tracers: a study on muscarinic acetylcholine receptors with N-[(11)C]methyl-4-piperidylbenzilate.
The present work demonstrates quantitative autoradiography by using positron emission tomography tracers and storage phosphorimaging plates. The uptake and association of [(11)C]N-methyl-4-piperidylbenzilate was measured in rat brain tissue cryosections of various thicknesses. The signal increased with increasing section thickness, but only in 10-micrometer-thick sections did the binding reach the steady state during a 50-min observation time. This violation of the equilibrium condition, potentially combined with perfusion limitations, leads to erroneous increased binding-site density and decreased affinity in the 25- and 50-micrometer-thick sections. For better imaging of receptor distribution it is reasonable to use thicker sections. For quantitative analysis of receptor-binding parameters, the specific properties of ligands at different thicknesses of cryosections need to be considered. Evidence is provided that the nonselective muscarinic antagonist N-methyl-4-piperidylbenzilate binds preferentially to the M(4) subtype of muscarinic acetylcholine receptors.
Department of Neuroscience, Unit of Pharmacology, Faculty of Medicine, Uppsala University, Uppsala, Sweden.
S
S
Sihver
W
W
Sihver
M
M
Bergström
A U
AU
Höglund
P
P
Sjöberg
B
B
Lângström
Y
Y
Watanabe
D000818:Animals; D001345:Autoradiography; D001561:Benzilates / Q000378:metabolism* / Q000493:pharmacokinetics; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D006207:Half-Life; D007091:Image Processing, Computer-Assisted; D008297:Male; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013116:Spinal Cord / Q000000981:diagnostic imaging / Q000378:metabolism; D014055:Tomography, Emission-Computed
D001561:Benzilates; D010880:Piperidines; D019275:Radiopharmaceuticals; D011976:Receptors, Muscarinic; C020407:enpiperate