In vivo visualization of central muscarinic receptors using [11C]quinuclidinyl benzilate and positron emission tomography in baboons

Eur J Pharmacol. 1992 Mar 24;213(2):275-84. doi: 10.1016/0014-2999(92)90692-w.

Abstract

The muscarinic antagonist, quinuclidinyl benzilate (QNB), labeled with carbon 11 was used as a radioligand to visualize in vivo by positron emission tomography (PET) the central muscarinic acetylcholine receptors (mAChR) in baboons (Papio papio). The binding characteristics of [11C]QNB showed its specific binding to central mAChR. [11C]QNB brain uptake was high in cerebral cortex and striatum, areas that are rich in mAChR, whereas it decreased rapidly in cerebellum, evidencing non-specific binding in this structure that is almost devoid of mAChR. These results are consistent with the known cerebral distribution of mAChR in primates. [11C]QNB specific cerebral binding was enhanced by pretreatment with methyl-QNB, a peripherally acting muscarinic antagonist. Specifically labeled binding sites alone were blocked by prior administration of dexetimide, a muscarinic antagonist. Specific radioactivity was driven out from mAChR-rich regions by atropine and dexetimide, drugs with high affinity for mAChR. This competition was stereospecific since only dexetimide, the pharmacologically active isomer of benzetimide, was able to compete with the radioligand on its binding sites. A relationship between the occupancy of [11C]QNB-labeled receptors by atropine or dexetimide and the concomitant induction of a pharmacological effect was also detected by simultaneous PET scanning and electroencephalographic recording. Since mAChR form an important part of choline receptors in the central nervous system, [11C]QNB appears to be a suitable radiotracer to monitor cerebral physiological or pathological phenomena linked to the cholinergic system in living subjects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Cerebral Cortex / chemistry*
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism
  • Dexetimide / pharmacology
  • Electroencephalography / drug effects
  • Male
  • Papio / metabolism
  • Quinuclidinyl Benzilate / metabolism*
  • Radioligand Assay
  • Receptors, Muscarinic / analysis*
  • Receptors, Muscarinic / metabolism
  • Tomography, Emission-Computed

Substances

  • Receptors, Muscarinic
  • Dexetimide
  • Quinuclidinyl Benzilate
  • Atropine