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Open AccessArticle
Radiosynthesis and Preclinical Evaluation of 18F-Labeled Estradiol Derivatives with Different Lipophilicity for PET Imaging of Breast Cancer
by
Anna Friedel
Anna Friedel 1,
Olaf Prante
Olaf Prante 1,2
and
Simone Maschauer
Simone Maschauer 1,*
1
Department of Nuclear Medicine, Molecular Imaging and Radiochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
2
FAU NeW—Research Center New Bioactive Compounds, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91058 Erlangen, Germany
*
Author to whom correspondence should be addressed.
Submission received: 19 June 2024
/
Revised: 19 July 2024
/
Accepted: 23 July 2024
/
Published: 24 July 2024
Simple Summary
Breast cancer is one of the most prevalent forms of cancer diagnosed in women worldwide. Since the estradiol receptor (ER) is overexpressed in 75% of breast tumors, it is a reasonable target for tumor diagnosis and therapy. This study focuses on the development and preclinical evaluation of readily synthesized 18F-labeled estradiol derivatives with different lipophilicity. The least hydrophilic derivative, 18F-TA-Glyco-EE, showed the highest cellular uptake in ER-positive breast cancer cells. The in vivo PET imaging of breast tumor-bearing mice demonstrated the desired rapid clearance of the tracer from the excretory organ through the liver. The in vitro autoradiography of ER-positive tumor sections confirmed the high specific binding of 18F-TA-Glyco-EE. In conclusion, 18F-TA-Glyco-EE may be a promising candidate for imaging of ER-positive breast cancer.
Abstract
About 75% of breast tumors show an overexpression of the estradiol receptor (ER), making it a valuable target for tumor diagnosis and therapy. To date, 16α-[18F]fluoroestradiol (FES) is the only FDA-approved imaging probe for the positron emission tomography (PET) imaging of ER-positive (ER+) breast cancer. However, FES has the drawback of a high retention in the liver. Therefore, the aim of this study was the development and preclinical evaluation of estradiol (E2) derivatives with different lipophilicity. Three 18F-labeled prosthetic groups (two glycosyl and one PEG azide) were chosen for conjugation with ethinyl estradiol (EE) by 18F-CuAAC (Cu-catalyzed azide-alkyne cycloaddition). The cellular uptake in ER+ MCF-7 tumor cells was highest for the less hydrophilic derivative (18F-TA-Glyco-EE). In nude mice bearing different breast tumors (ER+ MCF-7 and T47D versus ER− MDA-MB-231), 18F-TA-Glyco-EE revealed a high uptake in the liver (13%ID/g, 30 min p.i.), which decreased over 90 min to 1.2%ID/g, indicating fast hepatobiliary clearance. The statistically significant difference of 18F-TA-Glyco-EE uptake in T47D compared to MDA-MB-231 tumors at 60–90 min p.i. indicated ER-specific uptake, whereas in vivo PET imaging did not provide evidence for specific uptake of 18F-TA-Glyco-EE in MCF-7 tumors, probably due to ER occupation by E2 after E2-dependent MCF-7 tumor growth in mice. However, in vitro autoradiography revealed a high specific binding of 18F-TA-Glyco-EE to ER+ tumor slices. We conclude that 18F-TA-Glyco-EE, with its increased hydrophilicity after deacetylation in the blood and thus rapid washout from non-target tissues, may be a viable alternative to FES for the PET imaging of breast cancer.
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MDPI and ACS Style
Friedel, A.; Prante, O.; Maschauer, S.
Radiosynthesis and Preclinical Evaluation of 18F-Labeled Estradiol Derivatives with Different Lipophilicity for PET Imaging of Breast Cancer. Cancers 2024, 16, 2639.
https://doi.org/10.3390/cancers16152639
AMA Style
Friedel A, Prante O, Maschauer S.
Radiosynthesis and Preclinical Evaluation of 18F-Labeled Estradiol Derivatives with Different Lipophilicity for PET Imaging of Breast Cancer. Cancers. 2024; 16(15):2639.
https://doi.org/10.3390/cancers16152639
Chicago/Turabian Style
Friedel, Anna, Olaf Prante, and Simone Maschauer.
2024. "Radiosynthesis and Preclinical Evaluation of 18F-Labeled Estradiol Derivatives with Different Lipophilicity for PET Imaging of Breast Cancer" Cancers 16, no. 15: 2639.
https://doi.org/10.3390/cancers16152639
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