A novel solid phase synthesis of an estradiol derivative and preclinical evaluation for targeting estrogen-receptor positive breast cancer
Abstract [18F]-Fluoroestradiol, which is recently approved by the FDA, is a well-recognized estrogen receptor radiopharmaceutical in nuclear medicine to investigate both primary and metastatic breast cancers. This study introduces an innovative and effective method for synthesizing the DOTA-coupled...
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Nature Portfolio
2025-08-01
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| Online Access: | https://doi.org/10.1038/s41598-025-15367-0 |
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| author | Subhani M. Okarvi |
| author_facet | Subhani M. Okarvi |
| author_sort | Subhani M. Okarvi |
| collection | DOAJ |
| description | Abstract [18F]-Fluoroestradiol, which is recently approved by the FDA, is a well-recognized estrogen receptor radiopharmaceutical in nuclear medicine to investigate both primary and metastatic breast cancers. This study introduces an innovative and effective method for synthesizing the DOTA-coupled estradiol derivative and evaluating its preclinical potential. 68Ga/177Lu-labeled estradiol derivative was evaluated in vitro for its stability in human plasma, and binding capacity was determined using the ER-positive MCF-7 breast cancer cell line. In vivo, biodistribution and tumor targeting were conducted in ER-positive MCF-7 tumor-bearing nude mice. DOTA conjugated estradiol was prepared conveniently using solid-phase synthesis, and its radiolabeling with both 68Ga and 177Lu resulted in the formation of one major product, with high labeling efficiency (≥ 90%). Also, a high stability of the radiotracer was found in human plasma. The radiolabeled estradiol derivative exhibited a nanomolar affinity (< 20 nM) specific to the MCF-7 cell line. In the MCF-7 tumor xenograft model, the radioestradiol derivative displayed fast clearance from the blood and excretion mainly by the renal system. A rapid accumulation of 3.79% IA/g was observed in the MCF-7 tumors at 1 h p.i., whereas a low to moderate retention of radioactivity was seen in the normal organs, including the heart, lungs, liver, stomach, spleen, intestines, and kidneys (< 5% ID/g). The receptor specificity of the radioestradiol was confirmed by the receptor-blocking assay. The rapid and efficient targeting of tumors, along with the favorable pharmacokinetics, emphasizes the potential of radioestradiol for targeting tumors. Additionally, PET imaging demonstrated good visualization of MCF-7 tumors in nude mice. Our results indicate that the 68Ga/177Lu-labeled estradiol derivative could serve as a promising radiopharmaceutical option for the effective targeting of MCF-7 tumors. |
| format | Article |
| id | doaj-art-c1f6e676f57e4e9587740fc34fce86de |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-c1f6e676f57e4e9587740fc34fce86de2025-08-20T04:03:17ZengNature PortfolioScientific Reports2045-23222025-08-0115111410.1038/s41598-025-15367-0A novel solid phase synthesis of an estradiol derivative and preclinical evaluation for targeting estrogen-receptor positive breast cancerSubhani M. Okarvi0Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research CentreAbstract [18F]-Fluoroestradiol, which is recently approved by the FDA, is a well-recognized estrogen receptor radiopharmaceutical in nuclear medicine to investigate both primary and metastatic breast cancers. This study introduces an innovative and effective method for synthesizing the DOTA-coupled estradiol derivative and evaluating its preclinical potential. 68Ga/177Lu-labeled estradiol derivative was evaluated in vitro for its stability in human plasma, and binding capacity was determined using the ER-positive MCF-7 breast cancer cell line. In vivo, biodistribution and tumor targeting were conducted in ER-positive MCF-7 tumor-bearing nude mice. DOTA conjugated estradiol was prepared conveniently using solid-phase synthesis, and its radiolabeling with both 68Ga and 177Lu resulted in the formation of one major product, with high labeling efficiency (≥ 90%). Also, a high stability of the radiotracer was found in human plasma. The radiolabeled estradiol derivative exhibited a nanomolar affinity (< 20 nM) specific to the MCF-7 cell line. In the MCF-7 tumor xenograft model, the radioestradiol derivative displayed fast clearance from the blood and excretion mainly by the renal system. A rapid accumulation of 3.79% IA/g was observed in the MCF-7 tumors at 1 h p.i., whereas a low to moderate retention of radioactivity was seen in the normal organs, including the heart, lungs, liver, stomach, spleen, intestines, and kidneys (< 5% ID/g). The receptor specificity of the radioestradiol was confirmed by the receptor-blocking assay. The rapid and efficient targeting of tumors, along with the favorable pharmacokinetics, emphasizes the potential of radioestradiol for targeting tumors. Additionally, PET imaging demonstrated good visualization of MCF-7 tumors in nude mice. Our results indicate that the 68Ga/177Lu-labeled estradiol derivative could serve as a promising radiopharmaceutical option for the effective targeting of MCF-7 tumors.https://doi.org/10.1038/s41598-025-15367-0EstradiolEstrogen receptorBreast cancerRadiotheranosticTumor targeting. |
| spellingShingle | Subhani M. Okarvi A novel solid phase synthesis of an estradiol derivative and preclinical evaluation for targeting estrogen-receptor positive breast cancer Scientific Reports Estradiol Estrogen receptor Breast cancer Radiotheranostic Tumor targeting. |
| title | A novel solid phase synthesis of an estradiol derivative and preclinical evaluation for targeting estrogen-receptor positive breast cancer |
| title_full | A novel solid phase synthesis of an estradiol derivative and preclinical evaluation for targeting estrogen-receptor positive breast cancer |
| title_fullStr | A novel solid phase synthesis of an estradiol derivative and preclinical evaluation for targeting estrogen-receptor positive breast cancer |
| title_full_unstemmed | A novel solid phase synthesis of an estradiol derivative and preclinical evaluation for targeting estrogen-receptor positive breast cancer |
| title_short | A novel solid phase synthesis of an estradiol derivative and preclinical evaluation for targeting estrogen-receptor positive breast cancer |
| title_sort | novel solid phase synthesis of an estradiol derivative and preclinical evaluation for targeting estrogen receptor positive breast cancer |
| topic | Estradiol Estrogen receptor Breast cancer Radiotheranostic Tumor targeting. |
| url | https://doi.org/10.1038/s41598-025-15367-0 |
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