z-logo
Premium
Quantification of serotonin 5‐HT 1A receptors in monkey brain with [ 11 C]( R )‐(−)‐RWAY
Author(s) -
Yasuno Fumihiko,
Zoghbi Sami S.,
McCarron Julie A.,
Hong Jinsoo,
Ichise Masanori,
Brown Amira K.,
Gladding Robert L.,
Bacher John D.,
Pike Victor W.,
Innis Robert B.
Publication year - 2006
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20327
Subject(s) - serotonin , neuroscience , 5 ht receptor , receptor , psychology , 5 ht1a receptor , biology , biochemistry
[ 11 C]( R )‐(−)‐RWAY ([ 11 C]2, 3, 4, 5, 6, 7‐hexahydro‐1{4‐[1[4‐(2‐methoxyphenyl)‐piperazinyl]]‐2‐phenylbutyry}‐1 H ‐azepine) is a new radioligand for imaging brain 5‐HT 1A receptors with positron emission tomography. In [ 11 C]( R )‐(−)‐RWAY, the direction of the amide bond is expected to reduce metabolism by hydrolysis while allowing easy 11 C‐labeling at the methoxy position. The purposes of this study were to evaluate different tracer kinetic models in nonhuman primates to quantify 5‐HT 1A receptors with [ 11 C]( R )‐(−)‐RWAY and to test for the possible action of P‐glycoprotein (P‐gp), one of the known efflux pumps at the blood–brain barrier. The brain uptake of radioactivity from [ 11 C]( R )‐(−)‐RWAY into 5‐HT 1A receptor‐rich brain regions was severalfold greater than for its antipode ([ 11 C]( S )‐(+)‐RWAY) and could be displaced by receptor saturating doses of the selective 5‐HT 1A antagonist, WAY‐100635. Pretreatment with tariquidar, a potent inhibitor of P‐gp, increased brain uptake of [ 11 C]( R )‐(−)‐RWAY about 1.5‐fold and the plasma free fraction about 1.8‐fold. Thus, the effect of tariquidar on brain uptake may have been caused by displacement of the radioligand binding to plasma proteins. Mathematical modeling showed that the estimated values of regional binding potential were correlated strongly between two‐tissue compartment model and multilinear reference tissue model, and thus, supported the use of the cerebellum as a reference region. Synapse 60:510–520, 2006. Published 2006 Wiley‐Liss, Inc.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here