In vivo quantification by SPECT of [123I] ADAM bound to serotonin transporters in the brains of rabbits.
BACKGROUND
A novel radioiodine ligand [(123)I] ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine) has been suggested as a promising serotonin transporter (SERT) imaging agent for the central nervous system. In this study, the biodistribution of SERTs in the rabbit brain was investigated using [(123)I] ADAM and mapping images of the same animal produced by both single-photon emission computed tomography (SPECT) and microautoradiography. A semiquantification method was adopted to deduce the optimum time for SPECT imaging, whereas the input for a simple fully quantitative tracer kinetic model was provided from arterial blood sampling data.


METHODS
SPECT imaging was performed on female rabbits postinjection of 185 MBq [(123)I] ADAM. The time-activity curve obtained from the SPECT images was used to quantify the SERTs, for which the binding potential was calculated from the kinetic modeling of [(123)I] ADAM. The kinetic data were analyzed by the nonlinear least squares method. The effects of the selective serotonin reuptake inhibitors fluoxetine and p-chloroamphetamine (PCA) on rabbits were also evaluated. After scanning, the same animal was sacrificed and the brain was removed for microautoradiography. Regions-of-interest were analyzed using both SPECT and microautoradiography images. The SPECT images were coregistered manually with the corresponding microautoradiography images for comparative study.


RESULTS
During the time interval 90-100 min postinjection, the peak specific binding levels in different brain regions were compared and the brain stem was shown to have the highest activity. The target-to-background ratio was 1.89+/-0.02. Similar studies with fluoxetine and PCA showed a background level for SERT occupation. Microautoradiography demonstrated a higher level of anatomical details of the [(123)I] ADAM distribution than that obtained by SPECT imaging of the rabbit brain.


CONCLUSIONS
SPECT imaging of the rabbit brain with [(123)I] ADAM showed high affinity, high specificity, and favorable kinetics. The time-activity curve showed that the accumulation of the [(123)I] ADAM in the brain stem reached a maximum between 90 and 100 min postinjection. The microautoradiography provides high-resolution images of the rabbit brain. Our results for the [(123)I] ADAM biodistribution in the rabbit brains demonstrate that this new radioligand is suitable as a selective SPECT imaging agent for SERTs.
Ye
Xin-Xian
XX
Institute of Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan, ROC.
Hwang
Jeng-Jong
JJ
Hsieh
Jih-Fang
JF
Chen
Jyh-Cheng
JC
Chou
Yueh-Ting
YT
Tu
Kao-Yin
KY
Wey
Shiaw-Pyng
SP
Ting
Gann
G
D000465:Algorithms; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002928:Cinanserin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011985:Receptors, Serotonin / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
C413491:2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine; D019275:Radiopharmaceuticals; D011985:Receptors, Serotonin; D002928:Cinanserin