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

Bioorg Med Chem Lett. 2017 Aug 1;27(15):3460-3463. doi: 10.1016/j.bmcl.2017.05.079. Epub 2017 May 26.

Authors

Geng-Ying Li¹, Daria D Vaulina², Jia-Je Li¹, Olga S Fedorova², Hsin-Ell Wang¹, Ren-Shyan Liu³, Raisa N Krasikova⁴, Chuan-Lin Chen⁵

Affiliations

¹ Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
² N.P. Bechtereva Institute of Human Brain, Russian Academy of Science, Saint-Petersburg, Russian Federation.
³ Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Molecular and Genetic Imaging Core/Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan; National PET/Cyclotron Center and Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁴ N.P. Bechtereva Institute of Human Brain, Russian Academy of Science, Saint-Petersburg, Russian Federation; St.-Petersburg State University, Saint-Petersburg, Russian Federation. Electronic address: [email protected].
⁵ Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. Electronic address: [email protected].

PMID: 28619538
DOI: 10.1016/j.bmcl.2017.05.079

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 35GBq/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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Benzothiazoles / chemistry*
Benzothiazoles / pharmacokinetics
Breast / diagnostic imaging*
Breast Neoplasms / diagnostic imaging*
Cell Line, Tumor
Female
Fluorine Radioisotopes / chemistry*
Fluorine Radioisotopes / pharmacokinetics
Humans
Mice, Inbred NOD
Mice, SCID
Positron-Emission Tomography / methods*
Tissue Distribution

Substances

Benzothiazoles
Fluorine Radioisotopes