Gonadotropin-Releasing Hormone Receptor-Targeted Near-Infrared Fluorescence Probe for Specific Recognition and Localization of Peritoneal Metastases of Ovarian Cancer
Background: Peritoneal dissemination is common in advanced ovarian cancer. The completeness of cytoreduction is an independent prognostic factor. The intraoperative fluorescence imaging via tumor-specific near-infrared fluorophore might improve staging and surgical completeness. A promising target f...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00266/full |
| _version_ | 1819262913443004416 |
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| author | Qiyu Liu Qiyu Liu Qiyu Liu Xiaobo Zhou Wei Feng Tao Pu Tao Pu Tao Pu Xiaoping Li Fuyou Li Yu Kang Yu Kang Yu Kang Xiaoyan Zhang Xiaoyan Zhang Xiaoyan Zhang Congjian Xu Congjian Xu Congjian Xu |
| author_facet | Qiyu Liu Qiyu Liu Qiyu Liu Xiaobo Zhou Wei Feng Tao Pu Tao Pu Tao Pu Xiaoping Li Fuyou Li Yu Kang Yu Kang Yu Kang Xiaoyan Zhang Xiaoyan Zhang Xiaoyan Zhang Congjian Xu Congjian Xu Congjian Xu |
| author_sort | Qiyu Liu |
| collection | DOAJ |
| description | Background: Peritoneal dissemination is common in advanced ovarian cancer. The completeness of cytoreduction is an independent prognostic factor. The intraoperative fluorescence imaging via tumor-specific near-infrared fluorophore might improve staging and surgical completeness. A promising target for ovarian cancer is the gonadotropin-releasing hormone receptor (GnRHR). This study aimed to develop a GnRHR-targeted near-infrared imaging probe for the detection of peritoneal metastases of ovarian cancer.Methods: Indocyanine green (ICG) was conjugated with GnRH antagonist peptide to develop an ovarian cancer-selective fluorescence probe GnRHa-ICG. GnRHR expression was detected in ovarian cancer tissues. The binding capacity of GnRHa-ICG and ICG was detected in both cancer cell lines and mouse models of peritoneal metastatic ovarian cancer using fluorescence microscopy, flow cytometry, and near-infrared fluorescence imaging.Results: Tissue microarray analysis revealed the overexpression of GnRHR in ovarian cancer. GnRH-ICG exhibited the binding capacity in a panel of cancer cell lines with different expression levels of GnRHR. In ovarian cancer mouse models, GnRHa-ICG signals were detected in peritoneal tumor lesions rather than normal peritoneal and intestines tissues. ICG showed intensive fluorescence signals in intestines. The tumor-to-muscle ratio and tumor-to-intestine ratio of GnRHa-ICG was 7.41 ± 2.82 and 4.37 ± 1.66, higher than that of ICG (4.60 ± 0.50 and 0.57 ± 0.06) at 2 h post administration. The fluorescence signal of peritoneal metastases peaked in intensity at 2 h and maintained for up to 48 h. ICG also showed a weak signal in the tumor lesions due to the enhanced permeability and retention effect, but the intensity decreased quickly within 48 h.Conclusions: The developed GnRHR-targeted imaging agent GnRHa-ICG could specifically detected peritoneal tumor lesions from normal peritoneal and intestines tissues because of the modification of GnRHa to ICG. The plateau period of GnRHa-ICG accumulation may be feasible for clinical applications in fluorescence-guided surgery. Our GnRHR imaging concept may be effective in other hormone-related tumors with upregulated GnRHR expression. |
| first_indexed | 2024-12-23T20:05:15Z |
| format | Article |
| id | doaj.art-9912a4aa059c4c3599a652b181994088 |
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| language | English |
| last_indexed | 2024-12-23T20:05:15Z |
| publishDate | 2020-02-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-9912a4aa059c4c3599a652b1819940882022-12-21T17:32:57ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-02-011010.3389/fonc.2020.00266504643Gonadotropin-Releasing Hormone Receptor-Targeted Near-Infrared Fluorescence Probe for Specific Recognition and Localization of Peritoneal Metastases of Ovarian CancerQiyu Liu0Qiyu Liu1Qiyu Liu2Xiaobo Zhou3Wei Feng4Tao Pu5Tao Pu6Tao Pu7Xiaoping Li8Fuyou Li9Yu Kang10Yu Kang11Yu Kang12Xiaoyan Zhang13Xiaoyan Zhang14Xiaoyan Zhang15Congjian Xu16Congjian Xu17Congjian Xu18Obstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaDepartment of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, ChinaDepartment of Chemistry, Fudan University, Shanghai, ChinaDepartment of Chemistry, Fudan University, Shanghai, ChinaObstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaDepartment of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, ChinaDepartment of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, ChinaDepartment of Chemistry, Fudan University, Shanghai, ChinaObstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaDepartment of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, ChinaObstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaDepartment of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, ChinaObstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaDepartment of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, ChinaBackground: Peritoneal dissemination is common in advanced ovarian cancer. The completeness of cytoreduction is an independent prognostic factor. The intraoperative fluorescence imaging via tumor-specific near-infrared fluorophore might improve staging and surgical completeness. A promising target for ovarian cancer is the gonadotropin-releasing hormone receptor (GnRHR). This study aimed to develop a GnRHR-targeted near-infrared imaging probe for the detection of peritoneal metastases of ovarian cancer.Methods: Indocyanine green (ICG) was conjugated with GnRH antagonist peptide to develop an ovarian cancer-selective fluorescence probe GnRHa-ICG. GnRHR expression was detected in ovarian cancer tissues. The binding capacity of GnRHa-ICG and ICG was detected in both cancer cell lines and mouse models of peritoneal metastatic ovarian cancer using fluorescence microscopy, flow cytometry, and near-infrared fluorescence imaging.Results: Tissue microarray analysis revealed the overexpression of GnRHR in ovarian cancer. GnRH-ICG exhibited the binding capacity in a panel of cancer cell lines with different expression levels of GnRHR. In ovarian cancer mouse models, GnRHa-ICG signals were detected in peritoneal tumor lesions rather than normal peritoneal and intestines tissues. ICG showed intensive fluorescence signals in intestines. The tumor-to-muscle ratio and tumor-to-intestine ratio of GnRHa-ICG was 7.41 ± 2.82 and 4.37 ± 1.66, higher than that of ICG (4.60 ± 0.50 and 0.57 ± 0.06) at 2 h post administration. The fluorescence signal of peritoneal metastases peaked in intensity at 2 h and maintained for up to 48 h. ICG also showed a weak signal in the tumor lesions due to the enhanced permeability and retention effect, but the intensity decreased quickly within 48 h.Conclusions: The developed GnRHR-targeted imaging agent GnRHa-ICG could specifically detected peritoneal tumor lesions from normal peritoneal and intestines tissues because of the modification of GnRHa to ICG. The plateau period of GnRHa-ICG accumulation may be feasible for clinical applications in fluorescence-guided surgery. Our GnRHR imaging concept may be effective in other hormone-related tumors with upregulated GnRHR expression.https://www.frontiersin.org/article/10.3389/fonc.2020.00266/fulltargeted imagingnear-infrared fluorescencegonadotropin-releasing hormone receptorindocyanine greenovarian cancer |
| spellingShingle | Qiyu Liu Qiyu Liu Qiyu Liu Xiaobo Zhou Wei Feng Tao Pu Tao Pu Tao Pu Xiaoping Li Fuyou Li Yu Kang Yu Kang Yu Kang Xiaoyan Zhang Xiaoyan Zhang Xiaoyan Zhang Congjian Xu Congjian Xu Congjian Xu Gonadotropin-Releasing Hormone Receptor-Targeted Near-Infrared Fluorescence Probe for Specific Recognition and Localization of Peritoneal Metastases of Ovarian Cancer Frontiers in Oncology targeted imaging near-infrared fluorescence gonadotropin-releasing hormone receptor indocyanine green ovarian cancer |
| title | Gonadotropin-Releasing Hormone Receptor-Targeted Near-Infrared Fluorescence Probe for Specific Recognition and Localization of Peritoneal Metastases of Ovarian Cancer |
| title_full | Gonadotropin-Releasing Hormone Receptor-Targeted Near-Infrared Fluorescence Probe for Specific Recognition and Localization of Peritoneal Metastases of Ovarian Cancer |
| title_fullStr | Gonadotropin-Releasing Hormone Receptor-Targeted Near-Infrared Fluorescence Probe for Specific Recognition and Localization of Peritoneal Metastases of Ovarian Cancer |
| title_full_unstemmed | Gonadotropin-Releasing Hormone Receptor-Targeted Near-Infrared Fluorescence Probe for Specific Recognition and Localization of Peritoneal Metastases of Ovarian Cancer |
| title_short | Gonadotropin-Releasing Hormone Receptor-Targeted Near-Infrared Fluorescence Probe for Specific Recognition and Localization of Peritoneal Metastases of Ovarian Cancer |
| title_sort | gonadotropin releasing hormone receptor targeted near infrared fluorescence probe for specific recognition and localization of peritoneal metastases of ovarian cancer |
| topic | targeted imaging near-infrared fluorescence gonadotropin-releasing hormone receptor indocyanine green ovarian cancer |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.00266/full |
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