Positron emission tomography of 5-HT transporter sites in the baboon brain with [11C]McN5652.
[11C]McN5652 is a new radioligand specific for 5-hydroxytryptamine (5-HT; serotonin) transporters. In this study we used [11C]McN5652 to image the 5-HT transporter sites in baboon brain by positron emission tomography (PET). Dynamic PET studies were performed in three Papio anubis baboons. The animals were injected intravenously first with 11C-labeled (+)-McN5652([11C](+)McN5652), then with pharmacologically inactive enantiomer 11C-labeled (-)-McN5652 ([11C](-)McN5652); two animals received a third study with [11C](+)McN5652 after pretreatment with the specific 5-HT uptake site inhibitor fluoxetine (5 mg/kg). Initial uptake into the brain was similar for both [11C](+)McN5652 and [11C](-)McN5652. At later times (45-120 min after injection), only [11C](+)McN5652 showed a distribution characteristic for 5-HT uptake sites. In contrast, in studies with [11C](-)McN5652 and in those with [11C](+)McN5652 after 5-HT uptake site blockade with fluoxetine, 11C radioactivity concentrations were significantly lower and the distribution pattern was relatively even. The differences between [11C](+)-and (-)McN5652 were calculated for the time interval 95-125 min postinjection and used to estimate specific binding. Specific binding correlated well (r = 0.95, p < 0.001) with the known density of 5-HT uptake sites in human brain. These results indicate that [11C](+)McN5652 is suitable for PET imaging of 5-HT uptake sites in primate brain.
Szabo
Z
Z
Department of Radiology, Johns Hospkins Medical Institutions, Baltimore, MD 21205, USA.
Scheffel
U
U
Suehiro
M
M
Dannals
R F
RF
Kim
S E
SE
Ravert
H T
HT
Ricaurte
G A
GA
Wagner
H N
HN
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D007546:Isoquinolines / Q000378:metabolism / Q000493:pharmacokinetics*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012702:Serotonin Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins; D013237:Stereoisomerism; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine; C058079:McN 5652