PMID: 8971856Oct 1, 1996Paper

Autoradiographic evidence that (R)-3-quinuclidinyl (S)-4-fluoromethylbenzilate ((R,S)-FMeQNB) displays in vivo selectivity for the muscarinic m2 subtype

Nuclear Medicine and Biology
S F BoulayW C Eckelman

Abstract

Alzheimer's disease (AD) involves selective loss of muscarinic m2, but not m1, subtype neuroreceptors in cortical and hippocampal regions of the human brain. Until recently, emission tomographic study of the loss of m2 receptors in AD has been limited by the absence of available m2-selective radioligands that can penetrate the blood-brain barrier. We now demonstrate the in vivo m2 selectivity of a fluorinated derivative of QNB, (R)-3-quinuclidinyl (S)-4-fluoromethylbenzilate ((R,S)-FMeQNB), by studying autoradiographically the in vivo inhibition of radioiodinated (R)-3-quinuclidinyl (S)-4-iodobenzilate ((R,S)-[125I]IQNB) binding by unlabelled (R,S)-FMeQNB. In the absence of (R,S)-FMeQNB, (R,S)-[125I]IQNB labels brain regions in proportion to the total muscarinic receptor concentration; in the presence of 75 nmol of (R,S)-FMeQNB, (R,S)-[125I]IQNB labelling in those brain regions containing predominantly m2 subtype is reduced to background levels. We conclude that (R,S)-FMeQNB is m2-selective in vivo, and that (R,S)-[18F]FMeQNB may be of potential use in positron emission tomographic (PET) study of the loss of m2 receptors in AD.

References

Jan 1, 1992·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·R P Hertzman, B R Zeeberg
Nov 1, 1990·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Y SawadaW Eckelman
Jul 17, 1995·The Journal of Comparative Neurology·C F HohmannA I Levey
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Apr 1, 1997·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·B R ZeebergR C Reba

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Citations

Mar 1, 2000·Toxicon : Official Journal of the International Society on Toxinology·D JerusalinskyC Cerveñansky
Aug 1, 1997·Bioorganic & Medicinal Chemistry·D O KiesewetterW C Eckelman
Aug 23, 2001·Nuclear Medicine and Biology·W C Eckelman
Mar 18, 2004·Neuroimaging Clinics of North America·Satoshi Minoshima

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