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Research ArticleArticle

Quantitative Autoradiography with Short-Lived Positron Emission Tomography Tracers: A Study on Muscarinic Acetylcholine Receptors withN-[11C]methyl-4-piperidylbenzilate

Sven Sihver, Wiebke Sihver, Mats Bergström, A. Urban Höglund, Pernilla Sjöberg, Bengt Långström and Yasuyoshi Watanabe
Journal of Pharmacology and Experimental Therapeutics August 1999, 290 (2) 917-922;
Sven Sihver
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Wiebke Sihver
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Mats Bergström
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A. Urban Höglund
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Pernilla Sjöberg
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Bengt Långström
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Yasuyoshi Watanabe
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Abstract

The present work demonstrates quantitative autoradiography by using positron emission tomography tracers and storage phosphorimaging plates. The uptake and association of [11C]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-μm-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-μm-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 antagonistN-methyl-4-piperidylbenzilate binds preferentially to the M4 subtype of muscarinic acetylcholine receptors.

Footnotes

  • Send reprint requests to: Mats Bergström, UAS, Uppsala University PET Centre, S-75185 Uppsala, Sweden. E-mail:mats.bergstrom{at}pet.uu.se

  • ↵1 This work is planned to be used in Sven Sihver’s Ph.D. thesis.

  • Abbreviations:
    PET
    positron emission tomography
    [11C]NMPB
    11C-labeledN-methyl-4-piperidylbenzilate
    ROI
    region of interest
    M1 to M5
    acetylcholine muscarinic receptor subtypes
    • Received January 15, 1999.
    • Accepted March 22, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 290 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 290, Issue 2
1 Aug 1999
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Research ArticleArticle

Quantitative Autoradiography with Short-Lived Positron Emission Tomography Tracers: A Study on Muscarinic Acetylcholine Receptors withN-[11C]methyl-4-piperidylbenzilate

Sven Sihver, Wiebke Sihver, Mats Bergström, A. Urban Höglund, Pernilla Sjöberg, Bengt Långström and Yasuyoshi Watanabe
Journal of Pharmacology and Experimental Therapeutics August 1, 1999, 290 (2) 917-922;

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Research ArticleArticle

Quantitative Autoradiography with Short-Lived Positron Emission Tomography Tracers: A Study on Muscarinic Acetylcholine Receptors withN-[11C]methyl-4-piperidylbenzilate

Sven Sihver, Wiebke Sihver, Mats Bergström, A. Urban Höglund, Pernilla Sjöberg, Bengt Långström and Yasuyoshi Watanabe
Journal of Pharmacology and Experimental Therapeutics August 1, 1999, 290 (2) 917-922;
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