Imaging the availability of serotonin transporter in rat brain with 123I-ADAM and small-animal SPECT.
BACKGROUND
Imaging serotonin transporters during antidepressant treatment in small animals is a useful tool for preclinical study during drug development. In this work, we aimed to demonstrate the feasibility of using 123I-ADAM and small-animal SPECT to monitor serotonin transporter availabilities in rat brains prior to and after administration of a selective serotonin re-uptake inhibitor.


METHODS
Male Sprague-Dawley rats with and without administration of citalopram (4 mg x kg body weight) were examined in this study. During the process rat brains were scanned using a double-headed microSPECT system equipped with pinhole collimators. SPECT tomographic images and X-ray computed tomography (CT) were acquired after introducing 123I-ADAM via the tail vein. The 123I-ADAM specific binding was assessed by SPECT/CT fused image to draw regions of interest in the midbrain and cerebellum. Ex-vivo autoradiography was carried out as a parallel investigation to validate the SPECT technique.


RESULTS
SPECT images displayed specific binding ratio in midbrain to be 0.91+/-0.30 averaged from three rats. Drug occupancies (95.47+/-1.56)% were shown after administration of citalopram in a dosage of 4 mg x kg.


CONCLUSIONS
This study demonstrated that the serotonin transporter availability during antidepressant treatment in small animals can be assessed semi-quantitatively by using 123I-ADAM and SPECT.
Hwang
Li-Chung
LC
Radiation A, Institute of Nuclear Energy Research, Taoyuan, Taiwan. lchwang@iner.gov.tw
Chang
Chia-Jung
CJ
Liu
Hsueh-Hsuan
HH
Kao
Hung-Chun
HC
Lee
Shih-Ying
SY
Jan
Meei-Ling
ML
Chen
Chia-Chieh
CC
D000818:Animals; D002531:Cerebellum / Q000000981:diagnostic imaging* / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology; D005240:Feasibility Studies; D008297:Male; D008636:Mesencephalon / Q000000981:diagnostic imaging* / Q000187:drug effects; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
D015283:Citalopram; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors