In vivo quantification by SPECT of [ 123I] ADAM bound to serotonin transporters in the brains of rabbits

Xin Xian Ye, Jeng Jong Hwang, Jih Fang Hsieh, Jyh Cheng Chen, Yueh Ting Chou, Kao Yin Tu, Shiaw Pyng Wey, Gann Ting

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3 Scopus citations


A novel radioiodine ligand [ 123I] 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 [ 123I] 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. SPECT imaging was performed on female rabbits postinjection of 185 MBq [ 123I] 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 [ 123I] 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. 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 [ 123I] ADAM distribution than that obtained by SPECT imaging of the rabbit brain. SPECT imaging of the rabbit brain with [ 123I] ADAM showed high affinity, high specificity, and favorable kinetics. The time-activity curve showed that the accumulation of the [ 123I] 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 [ 123I] ADAM biodistribution in the rabbit brains demonstrate that this new radioligand is suitable as a selective SPECT imaging agent for SERTs.

Original languageEnglish
Pages (from-to)995-1003
Number of pages9
JournalNuclear Medicine and Biology
Issue number8
StatePublished - Nov 2004


  • [ I] ADAM
  • Microautoradiography
  • Serotonin transporters


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