A Near-Infrared Fluorescent Probe for Specific Imaging of Lymph Node Metastases in Ovarian Cancer via Active Targeting of the Gonadotropin-Releasing Hormone Receptor
Lymph node metastases are common in advanced ovarian cancer and are associated with poor prognosis. Accurate intraoperative identification of lymph node metastases remains a challenge in ovarian cancer surgery due to the lack of tumor-specific intraoperative imaging tools. Here, we developed a gonad...
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2025-06-01
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| author | Qiyu Liu Jiaan Sun Xiaobo Zhou Mingxing Zhang Tao Pu Xiaolan Gao Meng Zhang Congjian Xu Xiaoyan Zhang |
| author_facet | Qiyu Liu Jiaan Sun Xiaobo Zhou Mingxing Zhang Tao Pu Xiaolan Gao Meng Zhang Congjian Xu Xiaoyan Zhang |
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| description | Lymph node metastases are common in advanced ovarian cancer and are associated with poor prognosis. Accurate intraoperative identification of lymph node metastases remains a challenge in ovarian cancer surgery due to the lack of tumor-specific intraoperative imaging tools. Here, we developed a gonadotropin-releasing hormone receptor (GnRHR)-targeted near-infrared (NIR) fluorescent probe, GnRHa-PEG-Rh760, through conjugation of a GnRH analog peptide with the Rh760 fluorophore and polyethylene glycol (PEG). A non-targeted probe (PEG-Rh760) served as control. In mouse models of subcutaneous xenografts, peritoneal and lymph node metastases derived from ovarian cancer cells, GnRHa-PEG-Rh760 showed superior tumor-specific accumulation. NIR fluorescence imaging revealed strong fluorescence signals localized to primary tumors, peritoneal lesions, and metastatic lymph nodes with no off-target signals in normal lymph nodes. The spatial co-localization between the NIR fluorescence of GnRHa-PEG-Rh760 and tumor-derived bioluminescence clearly confirmed the probe’s target specificity. GnRHa-PEG-Rh760 mainly accumulated in the tumor and liver and was gradually cleared at 96 h post-injection. The retention of fluorescence signals in normal ovary tissue further validated GnRHR-mediated binding of the probe. Notably, GnRHa-PEG-Rh760 exhibited excellent biocompatibility with no observed systemic toxicity as evidenced by hematologic and histopathologic analyses. These data demonstrate the potential of GnRHa-PEG-Rh760 as an intraoperative imaging agent, providing real-time fluorescence imaging guidance to optimize surgical precision. This study highlights the value of receptor-targeted molecular imaging probes in precision cancer surgery. |
| format | Article |
| id | doaj-art-ac082f11773540aab1dab6dabfe90539 |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-06-01 |
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| series | Biomolecules |
| spelling | doaj-art-ac082f11773540aab1dab6dabfe905392025-08-20T02:24:23ZengMDPI AGBiomolecules2218-273X2025-06-0115686810.3390/biom15060868A Near-Infrared Fluorescent Probe for Specific Imaging of Lymph Node Metastases in Ovarian Cancer via Active Targeting of the Gonadotropin-Releasing Hormone ReceptorQiyu Liu0Jiaan Sun1Xiaobo Zhou2Mingxing Zhang3Tao Pu4Xiaolan Gao5Meng Zhang6Congjian Xu7Xiaoyan Zhang8 Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, ChinaDepartment of Chemistry, Fudan University, Shanghai 200438, China Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, ChinaLymph node metastases are common in advanced ovarian cancer and are associated with poor prognosis. Accurate intraoperative identification of lymph node metastases remains a challenge in ovarian cancer surgery due to the lack of tumor-specific intraoperative imaging tools. Here, we developed a gonadotropin-releasing hormone receptor (GnRHR)-targeted near-infrared (NIR) fluorescent probe, GnRHa-PEG-Rh760, through conjugation of a GnRH analog peptide with the Rh760 fluorophore and polyethylene glycol (PEG). A non-targeted probe (PEG-Rh760) served as control. In mouse models of subcutaneous xenografts, peritoneal and lymph node metastases derived from ovarian cancer cells, GnRHa-PEG-Rh760 showed superior tumor-specific accumulation. NIR fluorescence imaging revealed strong fluorescence signals localized to primary tumors, peritoneal lesions, and metastatic lymph nodes with no off-target signals in normal lymph nodes. The spatial co-localization between the NIR fluorescence of GnRHa-PEG-Rh760 and tumor-derived bioluminescence clearly confirmed the probe’s target specificity. GnRHa-PEG-Rh760 mainly accumulated in the tumor and liver and was gradually cleared at 96 h post-injection. The retention of fluorescence signals in normal ovary tissue further validated GnRHR-mediated binding of the probe. Notably, GnRHa-PEG-Rh760 exhibited excellent biocompatibility with no observed systemic toxicity as evidenced by hematologic and histopathologic analyses. These data demonstrate the potential of GnRHa-PEG-Rh760 as an intraoperative imaging agent, providing real-time fluorescence imaging guidance to optimize surgical precision. This study highlights the value of receptor-targeted molecular imaging probes in precision cancer surgery.https://www.mdpi.com/2218-273X/15/6/868intraoperative imaging agentstumor targetingovarian cancergonadotropin-releasing hormonelymph node metastasis |
| spellingShingle | Qiyu Liu Jiaan Sun Xiaobo Zhou Mingxing Zhang Tao Pu Xiaolan Gao Meng Zhang Congjian Xu Xiaoyan Zhang A Near-Infrared Fluorescent Probe for Specific Imaging of Lymph Node Metastases in Ovarian Cancer via Active Targeting of the Gonadotropin-Releasing Hormone Receptor Biomolecules intraoperative imaging agents tumor targeting ovarian cancer gonadotropin-releasing hormone lymph node metastasis |
| title | A Near-Infrared Fluorescent Probe for Specific Imaging of Lymph Node Metastases in Ovarian Cancer via Active Targeting of the Gonadotropin-Releasing Hormone Receptor |
| title_full | A Near-Infrared Fluorescent Probe for Specific Imaging of Lymph Node Metastases in Ovarian Cancer via Active Targeting of the Gonadotropin-Releasing Hormone Receptor |
| title_fullStr | A Near-Infrared Fluorescent Probe for Specific Imaging of Lymph Node Metastases in Ovarian Cancer via Active Targeting of the Gonadotropin-Releasing Hormone Receptor |
| title_full_unstemmed | A Near-Infrared Fluorescent Probe for Specific Imaging of Lymph Node Metastases in Ovarian Cancer via Active Targeting of the Gonadotropin-Releasing Hormone Receptor |
| title_short | A Near-Infrared Fluorescent Probe for Specific Imaging of Lymph Node Metastases in Ovarian Cancer via Active Targeting of the Gonadotropin-Releasing Hormone Receptor |
| title_sort | near infrared fluorescent probe for specific imaging of lymph node metastases in ovarian cancer via active targeting of the gonadotropin releasing hormone receptor |
| topic | intraoperative imaging agents tumor targeting ovarian cancer gonadotropin-releasing hormone lymph node metastasis |
| url | https://www.mdpi.com/2218-273X/15/6/868 |
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