Exploring the Application of Bifunctional Metal Chelators in Treating Triple-Negative Breast Cancer
Purpose: In this study, we independently synthesised and labelled a novel bidentate bifunctional chelating agent, 177Lu-3,4-HOPO-Cetuximab, that achieved tight binding between targeting and radioactivity, and evaluated its targeted killing ability of cells in vitro and in vivo.Method: 3,4-HOPO was s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2021.697862/full |
| _version_ | 1819130902003843072 |
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| author | Kuo Li Kuo Li Youjiu Zhang Xiaomei Wang Ran Zhu Changsheng Ma Rui Hu |
| author_facet | Kuo Li Kuo Li Youjiu Zhang Xiaomei Wang Ran Zhu Changsheng Ma Rui Hu |
| author_sort | Kuo Li |
| collection | DOAJ |
| description | Purpose: In this study, we independently synthesised and labelled a novel bidentate bifunctional chelating agent, 177Lu-3,4-HOPO-Cetuximab, that achieved tight binding between targeting and radioactivity, and evaluated its targeted killing ability of cells in vitro and in vivo.Method: 3,4-HOPO was successfully synthesised through a series of chemical steps using malt phenol as the raw material, which was then coupled with Cetuximab labelled with 177Lu. 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab was tested for its cell viability and cell-binding rate after different times and at different doses by CCK-8 and cell-binding experiments. 177Lu-3,4-HOPO-Cetuximab (~500 μCi) and 177Lu-DOTA-Cetuximab (~500 μCi) were injected into the tail vein of a subcutaneous metastasis mouse model of triple-negative breast cancer with a single injection, and tumour volume growth and body weight changes were regularly monitored for 20 days. The radioactivity distribution in nude mice was analysed after sacrifice, and the treated and untreated tumour tissues were analysed by HE staining.Result: The cell viability of 177Lu-3,4-HOPO-Cetuximab declined exponentially after treatment for 48 h at 50 Bq/mL to 500 kBq/mL, respectively; the cell activity was slowed down from 8 to 96 h at a dose of 500 kBq; while the binding rate of 4T1 cells in 177Lu-3,4-HOPO-Cetuximab from 1 to 24 h, respectively, increased logarithmically, which was similar with 177Lu-DOTA-Cetuximab. After 20 days of treatment, the body weight of nude mice with 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab were hardly changed, while the body weight with physiological saline decreased significantly. The tumour inhibition rate of the 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab were (37.03 ± 11.16)% and (38.7 ± 5.1)%; HE staining showed that tumour cells were affected by the action of 177Lu causing necrosis.Conclusion: The experiments showed that 177Lu-3,4-HOPO-Cetuximab has a certain targeted therapeutic ability for triple-negative breast cancer, and it is expected to become a potential targeted nuclear medicine treatment for triple-negative breast cancer. |
| first_indexed | 2024-12-22T09:06:59Z |
| format | Article |
| id | doaj.art-e879fc4e5423429a840e8609dce3b4f8 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-22T09:06:59Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-e879fc4e5423429a840e8609dce3b4f82022-12-21T18:31:35ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-08-01910.3389/fbioe.2021.697862697862Exploring the Application of Bifunctional Metal Chelators in Treating Triple-Negative Breast CancerKuo Li0Kuo Li1Youjiu Zhang2Xiaomei Wang3Ran Zhu4Changsheng Ma5Rui Hu6Department of Radiotherapy, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaSchool of Radiation Medicine and Protection, Soochow University, Suzhou, ChinaSchool of Radiation Medicine and Protection, Soochow University, Suzhou, ChinaSchool of Radiation Medicine and Protection, Soochow University, Suzhou, ChinaSchool of Radiation Medicine and Protection, Soochow University, Suzhou, ChinaDepartment of Radiotherapy, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, ChinaDepartment of Radiation Oncology, Suzhou Municipal Hospital, Suzhou, ChinaPurpose: In this study, we independently synthesised and labelled a novel bidentate bifunctional chelating agent, 177Lu-3,4-HOPO-Cetuximab, that achieved tight binding between targeting and radioactivity, and evaluated its targeted killing ability of cells in vitro and in vivo.Method: 3,4-HOPO was successfully synthesised through a series of chemical steps using malt phenol as the raw material, which was then coupled with Cetuximab labelled with 177Lu. 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab was tested for its cell viability and cell-binding rate after different times and at different doses by CCK-8 and cell-binding experiments. 177Lu-3,4-HOPO-Cetuximab (~500 μCi) and 177Lu-DOTA-Cetuximab (~500 μCi) were injected into the tail vein of a subcutaneous metastasis mouse model of triple-negative breast cancer with a single injection, and tumour volume growth and body weight changes were regularly monitored for 20 days. The radioactivity distribution in nude mice was analysed after sacrifice, and the treated and untreated tumour tissues were analysed by HE staining.Result: The cell viability of 177Lu-3,4-HOPO-Cetuximab declined exponentially after treatment for 48 h at 50 Bq/mL to 500 kBq/mL, respectively; the cell activity was slowed down from 8 to 96 h at a dose of 500 kBq; while the binding rate of 4T1 cells in 177Lu-3,4-HOPO-Cetuximab from 1 to 24 h, respectively, increased logarithmically, which was similar with 177Lu-DOTA-Cetuximab. After 20 days of treatment, the body weight of nude mice with 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab were hardly changed, while the body weight with physiological saline decreased significantly. The tumour inhibition rate of the 177Lu-3,4-HOPO-Cetuximab and 177Lu-DOTA-Cetuximab were (37.03 ± 11.16)% and (38.7 ± 5.1)%; HE staining showed that tumour cells were affected by the action of 177Lu causing necrosis.Conclusion: The experiments showed that 177Lu-3,4-HOPO-Cetuximab has a certain targeted therapeutic ability for triple-negative breast cancer, and it is expected to become a potential targeted nuclear medicine treatment for triple-negative breast cancer.https://www.frontiersin.org/articles/10.3389/fbioe.2021.697862/fulltriple negative breast cancerbifunctional chelatorcetuximabtargeted internal irradiation therapyHOPO |
| spellingShingle | Kuo Li Kuo Li Youjiu Zhang Xiaomei Wang Ran Zhu Changsheng Ma Rui Hu Exploring the Application of Bifunctional Metal Chelators in Treating Triple-Negative Breast Cancer Frontiers in Bioengineering and Biotechnology triple negative breast cancer bifunctional chelator cetuximab targeted internal irradiation therapy HOPO |
| title | Exploring the Application of Bifunctional Metal Chelators in Treating Triple-Negative Breast Cancer |
| title_full | Exploring the Application of Bifunctional Metal Chelators in Treating Triple-Negative Breast Cancer |
| title_fullStr | Exploring the Application of Bifunctional Metal Chelators in Treating Triple-Negative Breast Cancer |
| title_full_unstemmed | Exploring the Application of Bifunctional Metal Chelators in Treating Triple-Negative Breast Cancer |
| title_short | Exploring the Application of Bifunctional Metal Chelators in Treating Triple-Negative Breast Cancer |
| title_sort | exploring the application of bifunctional metal chelators in treating triple negative breast cancer |
| topic | triple negative breast cancer bifunctional chelator cetuximab targeted internal irradiation therapy HOPO |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2021.697862/full |
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