Positron emission tomography of 5-HT reuptake sites in the human brain with C-11 McN5652 extraction of characteristic images by artificial neural network analysis.
The goal of this work was to identify the distribution of serotonin transporters in the human brain with [11C](+)McN5652/PET. Four healthy volunteers were studied. To determine non-specific binding, a PET study was also performed with the inactive enantiomer [11C](-)McN5652 as well as with [11C](+)McN5652 after pretreatment with fluoxetine. For pattern extraction the PET data sets were analyzed by a back-propagation neural network. Two pharmacokinetic patterns and two characteristic images were separated; one representing specific binding, the other representing non-specific binding. The specific binding image showed characteristic distribution of serotonin transporters with [11C](+)McN5652. The pattern images demonstrated an improvement in image quality compared to the original PET images (reduced variance, higher region-to-cerebellum ratio, good correlation with known density of serotonin transporters). The non-specific binding images extracted from [11C](-)McN5652/PET were similar to those of [11C](-)McN5652 and [11C](-)McN5652 with fluoxetine. Thus, PET studies obtained with [11C](+)McN5652 largely represent the regional distribution of the serotonin transporters and the inactive enantiomer [11C](-)McN5652 shows the distribution of its nonspecific binding.
Szabo
Z
Z
Divisions of Nyclear Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Kao
P F
PF
Mathews
W B
WB
Ravert
H T
HT
Musachio
J L
JL
Scheffel
U
U
Dannals
R F
RF
D000328:Adult; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation*; D007546:Isoquinolines / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016571:Neural Networks, Computer; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins; D014055:Tomography, Emission-Computed / Q000295:instrumentation*
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; C058079:McN 5652