Quantitative autoradiography with short-lived positron emission tomography tracers: a study on muscarinic acetylcholine receptors with N-[(11)C]methyl-4-piperidylbenzilate

J Pharmacol Exp Ther. 1999 Aug;290(2):917-22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Benzilates / metabolism*
  • Benzilates / pharmacokinetics
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism
  • Half-Life
  • Image Processing, Computer-Assisted
  • Male
  • Neostriatum / diagnostic imaging
  • Neostriatum / metabolism
  • Piperidines / metabolism*
  • Piperidines / pharmacokinetics
  • Radiopharmaceuticals / metabolism*
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Muscarinic / metabolism*
  • Spinal Cord / diagnostic imaging
  • Spinal Cord / metabolism
  • Tomography, Emission-Computed

Substances

  • Benzilates
  • Piperidines
  • Radiopharmaceuticals
  • Receptors, Muscarinic
  • enpiperate