Imaging serotonin transporters with 123I-ADAM brain SPECT in healthy non-human primates.
BACKGROUND
Serotonin transporters (SERTs) play a major role in modulating serotonergic neuronal function and are the target of many antidepressant drugs used in neuro-psychiatric disorders. To gain more information on the temporal distribution of SERTs, 2-([2-([dimethylamino]methyl)phenoxyl]thio)-5-[I]iodophenylamine (I-ADAM) single photon emission computed tomography (SPECT) was utilized in an in vivo imaging study using non-human primates.


METHODS
Two female monkeys (Macaca cyclopis) were studied. Eight brain SPECT imaging examinations, each 30 min in duration, were obtained after injection of 185 MBq of I-ADAM. Images were obtained using a dual-head gamma camera equipped with ultra-high resolution fan-beam collimators. In addition to visual inspection, the radio-uptake and specific uptake ratios (SURs) of midbrain (MB), thalamus (TH), striatum (ST), temporal and frontal cortices and the whole brain in reference to the corresponding magnetic resonance image at the eight time points were measured. The SUR of MB, using cerebellum (CB) as the reference tissue, was calculated as (MB - CB)/CB, in mean counts/pixel. The SURs of the other brain regions were similarly measured.


RESULTS
There was relatively high uptake of I-ADAM in the MB and TH, moderate uptake in ST, lower uptake in the cerebral cortex, and almost no uptake in the CB. The image of MB could be easily identified at the first 30 min time point. It appeared that the SURs of MB, TH and ST reached equilibrium around 210 min after injection. No adverse reactions of the primates were found during and after imaging. Brain distribution of I-ADAM in the primate appeared consistent with the known distribution of SERTs.


CONCLUSIONS
In conjunction with a high SUR in MB, TH and ST, we speculate that I-ADAM may be a potential radioligand for SPECT studies of serotonin transporters in humans.
Huang
Wen-Sheng
WS
Department of Nuclear Medicine, Tri-Service General Hospital, 325 Section 2, Cheng-Kung Road, Taipei 114, Taiwan, ROC. wshuang@ms22.url.com.tw
Ma
Kuo-Hsing
KH
Cheng
Cheng-Yi
CY
Chen
Cheng-Yu
CY
Fu
Ying-Kai
YK
Chou
Yuan-Hwa
YH
Wey
Shiaw-Pyng
SP
Liu
Jian-Chuan
JC
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002928:Cinanserin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008251:Macaca; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011323:Primates; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins; D014018:Tissue Distribution
C413491:2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D002928:Cinanserin