AUTORADIOGRAPHIC EVIDENCE THAT 3-QUINUCLIDINYL-4-FLUOROBENZILATE (FQNB) DISPLAYS IN-VIVO SELECTIVITY FOR THE M2 SUBTYPE

Alzheimer's disease (AD) involves selective loss of muscarinic m2, but not mi, subtype neuroreceptors in cortical and hippocampal regions of the human brain. Emission tomographic study of the loss of m2 recepto rs in AD is limited by the fact that there is currently no available m a-selective radioligand which can penetrate the blood-brain barrier. W e now demonstrate the in vivo m2 selectivity of a fluorine derivative of QNB (FQNB), by studying autoradiographically the in vivo inhibition of radioiodinated (R)-3-quinuclidinyl (S)-4-iodobenzilate ((R,S)-[I-1 25]IQNB) binding by unlabeled FQNB. In the absence of FQNB, (R,S)-[I-1 25]IQNB labels brain regions in proportion to the total muscarinic rec eptor concentration; in the presence of 30.0 nmol of racemic FQNB, (R, S)-[I-125]IQNB labeling in those brain regions containing predominantl y the m2 subtype is reduced to background levels. We conclude that FQN B is ma-selective in vivo and that [F-18]FQNB or a closely related ana logue may be of potential use in positron emission tomographic study o f the loss of m2 receptors in AD. (C) 1996 Academic Press, Inc.