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Autoradiographic evidence that QNB displays in vivo selectivity for the m2 subtype.

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. Emission tomographic study of the loss of m2 receptors in AD is limited by the fact that there is currently no available m2-selective radioligand which can penetrate the blood-brain barrier. We have previously reported the results of in vivo dissection studies, using both carrier-free and low specific activity [3H]QNB, which show that [3H]QNB exhibits a substantial in vivo m2 selectivity. Because of the expense of the radioligand and the long exposure time required for the X-ray film, performing a large number of direct in vivo autoradiographic studies using [3H]QNB is precluded. Therefore, we now confirm these results autoradiographically by studying the in vivo inhibition of radio-iodinated (R)-3-quinuclidinyl (S)-4-iodobenzilate ((R,S)-[125I]IQNB) binding by unlabeled QNB. In the absence of QNB, (R,S)-[125I]IQNB labels brain regions in proportion to the total muscarinic receptor concentration; in the presence of 15 nmol QNB, (R,S,)-[125I]IQNB labeling in those brain regions containing predominantly m2 subtype is reduced to background levels. We conclude that QNB is m2-selective in vivo and that a suitably radiolabeled derivative of QNB, possibly labeled with 18F, may be of potential use in positron emission tomographic study of the loss of m2 receptors in AD.

journal_name

Neuroimage

journal_title

NeuroImage

authors

McRee RC,Boulay SF,Sood VK,Cohen EI,Cohen VI,Gitler MS,Zeeberg BR,Gibson RE,Reba RC

doi

10.1006/nimg.1995.1008

subject

Has Abstract

pub_date

1995-03-01 00:00:00

pages

55-62

issue

1

eissn

1053-8119

issn

1095-9572

pii

S1053-8119(85)71008-7

journal_volume

2

pub_type

杂志文章

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