Characterization of 4-[ 18F]-ADAM as an imaging agent for SERT in non-human primate brain using PET: A dynamic study

Yu An Chen, Wen Sheng Huang, Yaoh Shiang Lin, Cheng Yi Cheng, Ren Shyan Liu, Shyh Jen Wang, I. Hsun Li, San Yuan Huang, Chyng Yann Shiue, Cheng Yu Chen, Kuo Hsing Ma

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Abstract

Introduction: Serotonin transporter (SERT) has been associated with many psychiatric diseases. This study investigated the biodistribution of a serotonin transporter imaging agent, N,N-dimethyl-2-(2-amino-4- 18F-fluorophenylthio)benzylamine (4-[ 18F]-ADAM), in nonhuman primate brain using positron emission tomography (PET). Methods: Six and four Macaca cyclopis monkeys were used to determine the transit time (i.e., time necessary to reach biodistribution equilibrium) and the reproducibility of 4-[ 18F]-ADAM biodistribution in the brain, respectively. The sensitivity and specificity of 4-[ 18F]-ADAM binding to SERT were evaluated in one monkey challenged with different doses of fluoxetine and one monkey treated with 3,4-methylendioxymethamphetamine (MDMA). Dynamic PET imaging was performed for 3 h after 4-[ 18F]-ADAM intravenous bolus injection. The specific uptake ratios (SURs) in the midbrain (MB), thalamus (TH), striatum (ST) and frontal cortex (FC) were calculated. Results: The distribution of 4-[ 18F]-ADAM reached equilibrium 120-150 min after injection. The mean SURs were 2.49±0.13 in MB, 1.59±0.17 in TH, 1.35±0.06 in ST and 0.34±0.03 in FC, and the minimum variability was shown 120-150 min after 4-[ 18F]-ADAM injection. Using SURs and intraclass coefficient of correlation, the test/retest variability was under 8% and above 0.8, respectively, in SERT-rich areas. Challenge with fluoxetin (0.75-2 mg) dose-dependently inhibited the SURs in various brain regions. 4-[ 18F]-ADAM binding was markedly reduced in the brain of an MDMA-treated monkey compared to that in brains of normal controls. Conclusion: 4-[ 18F]-ADAM appears to be a highly selective radioligand for imaging SERT in monkey brain.

Original languageEnglish
Pages (from-to)279-285
Number of pages7
JournalNuclear Medicine and Biology
Volume39
Issue number2
DOIs
Publication statusPublished - Feb 2012
Externally publishedYes

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Keywords

  • Biodistribution
  • Brain
  • Nonhuman primate or monkey
  • PET
  • Serotonin transporter
  • Transit time

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Chen, Y. A., Huang, W. S., Lin, Y. S., Cheng, C. Y., Liu, R. S., Wang, S. J., Li, I. H., Huang, S. Y., Shiue, C. Y., Chen, C. Y., & Ma, K. H. (2012). Characterization of 4-[ 18F]-ADAM as an imaging agent for SERT in non-human primate brain using PET: A dynamic study. Nuclear Medicine and Biology, 39(2), 279-285. https://doi.org/10.1016/j.nucmedbio.2011.08.002