Positron emission tomography imaging of serotonin transporters in the human brain using [11C](+)McN5652.
This paper presents the first Positron Emission Tomography (PET) images of the serotonin (5-hydroxytryptamine, 5-HT) transporter in the living human brain. PET imaging was performed in three healthy subjects after administration of [11C](+)McN5652 (the (+) enantiomer of trans-1,2,3,5,6,10 beta-hexahydro- 6-[4-(methylthio) phenyl]pyrrolo-[2,1-a] -isoquinolone), a radioligand previously shown to selectively label the 5-HT transporter in vivo in the mammalian (mouse and baboon) brain. To demonstrate the specificity of [11C](+)McN5652 binding, additional images were obtained in the same subjects after injection of [11C](-)McN5652, the pharmacologically inactive enantiomer, and, in two of the subjects, with [11C](+)McN5652 after pretreatment with the 5-HT uptake site blocker fluoxetine. Highest accumulation of [11C](+)McN5652 was observed in the midbrain, putamen, caudate nucleus, hypothalamus, and thalamus, regions known to contain high densities of 5-HT transporters. In these areas [11C](+)McN5652 concentrations rose steadily over 120 min. In contrast, with [11C](-)McN5652 and when the [11C](+)McN5652 binding was inhibited with fluoxetine, radioactivity concentrations declined after reaching a maximum (at 20 to 30 min). Inhibition studies with fluoxetine suggest that only with [11C](+)McN5652, there is specific binding. In the cerebellum, a region relatively void of 5-HT transporters, both [11C](+)McN5652 with and without fluoxetine block and [11C](-)McN5652 were released at approximately the same rate. The results of the studies indicate that [11C](+)McN5652 labels 5-HT transporter sites in the human brain. Quantitative PET imaging studies with this new tracer should provide valuable information on the status of these sites in health and disease.
Szabo
Z
Z
Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Kao
P F
PF
Scheffel
U
U
Suehiro
M
M
Mathews
W B
WB
Ravert
H T
HT
Musachio
J L
JL
Marenco
S
S
Kim
S E
SE
Ricaurte
G A
GA
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins; D013237:Stereoisomerism; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine; D012701:Serotonin; C058079:McN 5652