Synthesis and evaluation of [ 18F]Fluorobutyl ethacrynic amide: A potential PET tracer for studying glutathione transferase

Ho Lien Huang, Chun Nan Yeh, Kang Wei Chang, Jenn Tzong Chen, Kun Ju Lin, Li Wu Chiang, Kee Ching Jeng, Wei Ting Wang, Ken Hong Lim, Caleb Gonshen Chen, Kun I. Lin, Ying Cheng Huang, Wuu Jyh Lin, Tzu Chen Yen, Chung Shan Yu

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Abstract

[ 18F]Flurobutyl ethacrynic amide ([ 18F]FBuEA) was prepared from the precursor tosylate N-Boc-N-[4-(toluenesulfonyloxy)butyl] ethacrynic amide with a radiochemical yield of 3%, a specific activity of 48 GBq/μmol and radiochemical purity of 98%. Chemical conjugation of [ 18F]FBuEA with glutathione (GSH) via a self-coupling reaction and enzymatic conjugation under catalysis of glutathiontransferase alpha (GST-α) and π provided about 41% yields of radiochemical conjugated product [ 18F]FBuEA-GSH, 85% and 5-16%, respectively. The catalytic selectivity of this tracer toward GST-alpha was addressed. Positron emission tomography (PET) imaging of [ 18F]FBuEA in normal rats showed that a homogeneous pattern of radioactivity was distributed in the liver, suggesting a catalytic role of GST. By contrast, PET images of [ 18F]FBuEA in rats with thioacetamide-induced cholangiocarcinoma displayed a heterogeneous pattern of radioactive accumulation with cold spots in tumor lesions. PET imaging with [ 18F]FBuEA could be used for early diagnosis of hepatic tumor with a low GST activity as well as liver function.

Original languageEnglish
Pages (from-to)3998-4003
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number12
DOIs
Publication statusPublished - Jun 15 2012
Externally publishedYes

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Keywords

  • Cholangiocarcinoma
  • Cold spot
  • GST-α
  • Imaging
  • Tumor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Huang, H. L., Yeh, C. N., Chang, K. W., Chen, J. T., Lin, K. J., Chiang, L. W., Jeng, K. C., Wang, W. T., Lim, K. H., Chen, C. G., Lin, K. I., Huang, Y. C., Lin, W. J., Yen, T. C., & Yu, C. S. (2012). Synthesis and evaluation of [ 18F]Fluorobutyl ethacrynic amide: A potential PET tracer for studying glutathione transferase. Bioorganic and Medicinal Chemistry Letters, 22(12), 3998-4003. https://doi.org/10.1016/j.bmcl.2012.04.091