Synthesis and biological evaluation of 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy)benzothiazole ([18F]FEDBT) for PET imaging of breast cancer

Geng Ying Li; Daria D. Vaulina; Jia Je Li; Olga S. Fedorova; Hsin Ell Wang; Ren Shyan Liu; Raisa N. Krasikova; Chuan Lin Chen

doi:10.1016/j.bmcl.2017.05.079

Synthesis and biological evaluation of 2-(3,4-dimethoxyphenyl)-6-(2-[¹⁸F]fluoroethoxy)benzothiazole ([¹⁸F]FEDBT) for PET imaging of breast cancer

Geng Ying Li, Daria D. Vaulina, Jia Je Li, Olga S. Fedorova, Hsin Ell Wang, Ren Shyan Liu, Raisa N. Krasikova^*, Chuan Lin Chen

^*Corresponding author for this work

Department of Biomedical Imaging and Radiological Sciences

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

10 Scopus citations

Abstract

Given the ever-present demand for improved PET radiotracer in oncology imaging, we have synthesized 2-(3,4-dimethoxyphenyl)-6-(2-[¹⁸F]fluoroethoxy)benzothiazole ([¹⁸F]FEDBT), a fluorine-18-containing fluoroethylated benzothiazole to explore its utility as a PET imaging tracer. [¹⁸F]FEDBT was prepared via kryptofix-mediated nucleophilic substitution of the tosyl group precursor. Fractionated ethanol-based solid-phase (SPE cartridge-based) purification afforded [¹⁸F]FEDBT in 60% radiochemical yield (EOB), with radiochemical purity in excess of 98% and the specific activity was 35 GBq/μmol. The radiotracer displayed clearly higher cellular uptake ratio in various breast cancer cell lines MCF7, MDA-MB-468 and MDA-MB-231. However, both biodistribution and microPET studies have showed an higher abdominal accumulation of [¹⁸F]FEDMBT and the tumor/muscle ratio of 1.8 was observed in the MDA-MB-231 xenograft tumors mice model. Further the lipophilic improvement is needed for the reducement of hepatobilliary accumulation and to promote the tumor uptake for PET imaging of breast cancer.

Original language	English
Pages (from-to)	3460-3463
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	27
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2017.05.079
State	Published - 2017

Keywords

Benzothiazole
Breast cancer
Fluorine-18
Positron emission tomography

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10.1016/j.bmcl.2017.05.079

Cite this

Li, G. Y., Vaulina, D. D., Li, J. J., Fedorova, O. S., Wang, H. E., Liu, R. S., Krasikova, R. N., & Chen, C. L. (2017). Synthesis and biological evaluation of 2-(3,4-dimethoxyphenyl)-6-(2-[¹⁸F]fluoroethoxy)benzothiazole ([¹⁸F]FEDBT) for PET imaging of breast cancer. Bioorganic and Medicinal Chemistry Letters, 27(15), 3460-3463. https://doi.org/10.1016/j.bmcl.2017.05.079

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abstract = "Given the ever-present demand for improved PET radiotracer in oncology imaging, we have synthesized 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy)benzothiazole ([18F]FEDBT), a fluorine-18-containing fluoroethylated benzothiazole to explore its utility as a PET imaging tracer. [18F]FEDBT was prepared via kryptofix-mediated nucleophilic substitution of the tosyl group precursor. Fractionated ethanol-based solid-phase (SPE cartridge-based) purification afforded [18F]FEDBT in 60% radiochemical yield (EOB), with radiochemical purity in excess of 98% and the specific activity was 35 GBq/μmol. The radiotracer displayed clearly higher cellular uptake ratio in various breast cancer cell lines MCF7, MDA-MB-468 and MDA-MB-231. However, both biodistribution and microPET studies have showed an higher abdominal accumulation of [18F]FEDMBT and the tumor/muscle ratio of 1.8 was observed in the MDA-MB-231 xenograft tumors mice model. Further the lipophilic improvement is needed for the reducement of hepatobilliary accumulation and to promote the tumor uptake for PET imaging of breast cancer.",

keywords = "Benzothiazole, Breast cancer, Fluorine-18, Positron emission tomography",

author = "Li, {Geng Ying} and Vaulina, {Daria D.} and Li, {Jia Je} and Fedorova, {Olga S.} and Wang, {Hsin Ell} and Liu, {Ren Shyan} and Krasikova, {Raisa N.} and Chen, {Chuan Lin}",

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AU - Li, Geng Ying

AU - Vaulina, Daria D.

AU - Li, Jia Je

AU - Fedorova, Olga S.

AU - Wang, Hsin Ell

AU - Liu, Ren Shyan

AU - Krasikova, Raisa N.

AU - Chen, Chuan Lin

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AB - Given the ever-present demand for improved PET radiotracer in oncology imaging, we have synthesized 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy)benzothiazole ([18F]FEDBT), a fluorine-18-containing fluoroethylated benzothiazole to explore its utility as a PET imaging tracer. [18F]FEDBT was prepared via kryptofix-mediated nucleophilic substitution of the tosyl group precursor. Fractionated ethanol-based solid-phase (SPE cartridge-based) purification afforded [18F]FEDBT in 60% radiochemical yield (EOB), with radiochemical purity in excess of 98% and the specific activity was 35 GBq/μmol. The radiotracer displayed clearly higher cellular uptake ratio in various breast cancer cell lines MCF7, MDA-MB-468 and MDA-MB-231. However, both biodistribution and microPET studies have showed an higher abdominal accumulation of [18F]FEDMBT and the tumor/muscle ratio of 1.8 was observed in the MDA-MB-231 xenograft tumors mice model. Further the lipophilic improvement is needed for the reducement of hepatobilliary accumulation and to promote the tumor uptake for PET imaging of breast cancer.

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