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

doi:10.1016/j.bmcl.2012.04.091

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

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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 language	English
Pages (from-to)	3998-4003
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2012.04.091
Publication status	Published - Jun 15 2012
Externally published	Yes

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

Access to Document

10.1016/j.bmcl.2012.04.091

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

Huang, HL, Yeh, CN, Chang, KW, Chen, JT, Lin, KJ, Chiang, LW, Jeng, KC, Wang, WT, Lim, KH, Chen, CG, Lin, KI, Huang, YC, Lin, WJ, Yen, TC & Yu, CS 2012, 'Synthesis and evaluation of [ ¹⁸F]Fluorobutyl ethacrynic amide: A potential PET tracer for studying glutathione transferase', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 12, pp. 3998-4003. https://doi.org/10.1016/j.bmcl.2012.04.091

@article{ce7e54d7c1c14995833da3575567b70f,

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

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.",

keywords = "Cholangiocarcinoma, Cold spot, GST-α, Imaging, Tumor",

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

note = "Funding Information: We are grateful to the National Science Council of Taiwan, CGMH_NTHU Joint Research and Chang-Gung Medical Research Project for providing financial support of the Grant numbers of NSC-98-2113-M-007-012, NSC-97-2314-B-182A-020-MY3, CGTH96N2342E1, CMRPG390931, CMRPG391512 and CMRPG3B0361. Technical assistance by Mr. Yean-Hung Tu and Ms. Li-Yuan Huang are acknowledged. We acknowledge Dr. Shui-Tein Chen from Institute of Biological Chemistry at Academia Sinica for his review of this manuscript. ",

year = "2012",

month = jun,

day = "15",

doi = "10.1016/j.bmcl.2012.04.091",

language = "English",

volume = "22",

pages = "3998--4003",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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number = "12",

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TY - JOUR

T1 - Synthesis and evaluation of [ 18F]Fluorobutyl ethacrynic amide

T2 - A potential PET tracer for studying glutathione transferase

AU - Huang, Ho Lien

AU - Yeh, Chun Nan

AU - Chang, Kang Wei

AU - Chen, Jenn Tzong

AU - Lin, Kun Ju

AU - Chiang, Li Wu

AU - Jeng, Kee Ching

AU - Wang, Wei Ting

AU - Lim, Ken Hong

AU - Chen, Caleb Gonshen

AU - Lin, Kun I.

AU - Huang, Ying Cheng

AU - Lin, Wuu Jyh

AU - Yen, Tzu Chen

AU - Yu, Chung Shan

N1 - Funding Information: We are grateful to the National Science Council of Taiwan, CGMH_NTHU Joint Research and Chang-Gung Medical Research Project for providing financial support of the Grant numbers of NSC-98-2113-M-007-012, NSC-97-2314-B-182A-020-MY3, CGTH96N2342E1, CMRPG390931, CMRPG391512 and CMRPG3B0361. Technical assistance by Mr. Yean-Hung Tu and Ms. Li-Yuan Huang are acknowledged. We acknowledge Dr. Shui-Tein Chen from Institute of Biological Chemistry at Academia Sinica for his review of this manuscript.

PY - 2012/6/15

Y1 - 2012/6/15

N2 - [ 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.

AB - [ 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.

KW - Cholangiocarcinoma

KW - Cold spot

KW - GST-α

KW - Imaging

KW - Tumor

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