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

研究成果: 雜誌貢獻 › 文章

25 引文 (Scopus)

摘要

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.
原文英語
頁（從 - 到）279-285
頁數7
期刊Nuclear Medicine and Biology
卷39
發行號2
DOIs
出版狀態已發佈 - 二月 2012
對外發佈Yes

指紋

Serotonin Plasma Membrane Transport Proteins
Positron-Emission Tomography
Primates
Haplorhini
Brain
Fluoxetine
Frontal Lobe
Mesencephalon
Thalamus
Injections
Macaca
Intravenous Injections
Psychiatry
Sensitivity and Specificity

ASJC Scopus subject areas

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

引用此文

Characterization of 4-[ 18F]-ADAM as an imaging agent for SERT in non-human primate brain using PET : A dynamic study. / Chen, Yu An; Huang, Wen Sheng; Lin, Yaoh Shiang; Cheng, Cheng Yi; Liu, Ren Shyan; Wang, Shyh Jen; Li, I. Hsun; Huang, San Yuan; Shiue, Chyng Yann; Chen, Cheng Yu; Ma, Kuo Hsing.

於: Nuclear Medicine and Biology, 卷 39, 編號 2, 02.2012, p. 279-285.

研究成果: 雜誌貢獻 › 文章

Chen, YA, Huang, WS, Lin, YS, Cheng, CY, Liu, RS, Wang, SJ, Li, IH, Huang, SY, Shiue, CY, Chen, CY & Ma, KH 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, 卷 39, 編號 2, 頁 279-285. https://doi.org/10.1016/j.nucmedbio.2011.08.002
Chen YA, Huang WS, Lin YS, Cheng CY, Liu RS, Wang SJ 等. 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. 2012 2月;39(2):279-285. https://doi.org/10.1016/j.nucmedbio.2011.08.002
Chen, Yu An ; Huang, Wen Sheng ; Lin, Yaoh Shiang ; Cheng, Cheng Yi ; Liu, Ren Shyan ; Wang, Shyh Jen ; Li, I. Hsun ; Huang, San Yuan ; Shiue, Chyng Yann ; Chen, Cheng Yu ; Ma, Kuo Hsing. / Characterization of 4-[ 18F]-ADAM as an imaging agent for SERT in non-human primate brain using PET : A dynamic study. 於: Nuclear Medicine and Biology. 2012 ; 卷 39, 編號 2. 頁 279-285.
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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.",
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author = "Chen, {Yu An} and Huang, {Wen Sheng} and Lin, {Yaoh Shiang} and Cheng, {Cheng Yi} and Liu, {Ren Shyan} and Wang, {Shyh Jen} and Li, {I. Hsun} and Huang, {San Yuan} and Shiue, {Chyng Yann} and Chen, {Cheng Yu} and Ma, {Kuo Hsing}",
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T1 - Characterization of 4-[ 18F]-ADAM as an imaging agent for SERT in non-human primate brain using PET

T2 - A dynamic study

AU - Chen, Yu An

AU - Huang, Wen Sheng

AU - Lin, Yaoh Shiang

AU - Cheng, Cheng Yi

AU - Liu, Ren Shyan

AU - Wang, Shyh Jen

AU - Li, I. Hsun

AU - Huang, San Yuan

AU - Shiue, Chyng Yann

AU - Chen, Cheng Yu

AU - Ma, Kuo Hsing

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N2 - 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.

AB - 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.

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