[11C](+)McN5652 as a radiotracer for imaging serotonin uptake sites with PET.
The in vivo behavior of the stereoisomers of [11C]McN5652, a highly potent serotonin (5-HT) uptake blocker, was determined to evaluate their utility as radiotracers for imaging 5-HT uptake sites by positron emission tomography (PET). After intravenous injection into mice, [11C](+)McN5652 showed markedly higher uptake and longer retention in regions with high density of 5-HT uptake sites than the [11C]-labeled racemic mixture, while [11C](-)McN5652 washed out rapidly. With the [11C](+)-enantiomer, the ratio between hypothalamus and cerebellum reached 6 at 90 minutes. The binding of [11C](+)McN5652 was inhibited by 45-73% by pre-injection of 5 mg/kg of paroxetine, a selective 5-HT uptake blocker, in all regions examined except cerebellum where no significant effect of the drug was observed. [11C](-)McN5652 showed no specific binding in any of the regions. The [11C]-labeled cis isomer, [11C]McN5655, revealed surprisingly low brain penetration and showed no significantly higher uptake in regions of interest than cerebellum. These results suggest that [11C](+)McN5652 is a promising candidate as a PET radiotracer for studying 5-HT uptake sites in vivo.
Suehiro
M
M
Division of Nuclear Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2179.
Scheffel
U
U
Ravert
H T
HT
Dannals
R F
RF
Wagner
H N
HN
D000818:Animals; D001665:Binding Sites; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D007546:Isoquinolines / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000737:chemistry / Q000493:pharmacokinetics; D013237:Stereoisomerism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D007546:Isoquinolines; D012702:Serotonin Antagonists; D012701:Serotonin; C058079:McN 5652