Mucin 18‐targeted humanized monoclonal antibody immune positron emission tomography imaging and patient‐derived tumor xenograft visualization
Abstract In the context of precision diagnosis for various subtypes of melanoma, identifying biomarkers with clinical translational potential from a molecular standpoint is crucial for a more comprehensive characterization of the disease. Mucin 18 (MUC18) is highly expressed in both tumor cells and...
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2024-12-01
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| Online Access: | https://doi.org/10.1002/VIW.20240055 |
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| author | Qian Zhang Haizhen Du Xiuli Ma Song Liu Xiangxing Kong Muye Hu Jing Shi Yanfang Tang ShuHui Liu Xun Meng Qian Guo Yan Kong Jun Guo Bin Lian Zhi Yang Hua Zhu |
| author_facet | Qian Zhang Haizhen Du Xiuli Ma Song Liu Xiangxing Kong Muye Hu Jing Shi Yanfang Tang ShuHui Liu Xun Meng Qian Guo Yan Kong Jun Guo Bin Lian Zhi Yang Hua Zhu |
| author_sort | Qian Zhang |
| collection | DOAJ |
| description | Abstract In the context of precision diagnosis for various subtypes of melanoma, identifying biomarkers with clinical translational potential from a molecular standpoint is crucial for a more comprehensive characterization of the disease. Mucin 18 (MUC18) is highly expressed in both tumor cells and tumor vasculature in major melanoma subtypes and is restricted to normal tissues. A noninvasive imaging approach for MUC18 in melanoma utilizing an immune positron emission tomography (PET) radionuclide‐conjugated drug (RDC) with an 89Zr‐labeled humanized anti‐MUC18 monoclonal antibody (mAb) was developed. A375, Sk‐Mel‐28, HMVII, and A549 cells and tumor model mice were conducted. Immuno‐PET was employed to assess the specificity and targeting of three distinct melanoma cell line‐derived xenografts (CDXs) and patient‐derived tumor xenografts (PDXs) in immunodeficient mice. The developed RDC, named 89Zr‐IP150, demonstrated robust in vitro stability and high binding affinity, ensuring reliable and specific PET imaging of small, medium, and large subcutaneous tumors in human melanoma mouse xenotransplantation models. Notably, for the first time, the clinical translational potential of 89Zr‐IP150 was successfully validated using PDX models. These findings present a noninvasive, real‐time method for the early screening of MUC18 (+) melanoma patients and are important for studying the early‐stage biological distribution of MUC18‐targeted antibody‐drug conjugates. |
| format | Article |
| id | doaj-art-e77badb4bfd9401ba3bb7dd9447bd0d4 |
| institution | OA Journals |
| issn | 2688-3988 2688-268X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
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| spelling | doaj-art-e77badb4bfd9401ba3bb7dd9447bd0d42025-08-20T01:58:04ZengWileyView2688-39882688-268X2024-12-0156n/an/a10.1002/VIW.20240055Mucin 18‐targeted humanized monoclonal antibody immune positron emission tomography imaging and patient‐derived tumor xenograft visualizationQian Zhang0Haizhen Du1Xiuli Ma2Song Liu3Xiangxing Kong4Muye Hu5Jing Shi6Yanfang Tang7ShuHui Liu8Xun Meng9Qian Guo10Yan Kong11Jun Guo12Bin Lian13Zhi Yang14Hua Zhu15GuiZhou University Medical College Guiyang ChinaDepartment of Renal Cancer and Melanoma Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital and Institute Beijing ChinaDepartment of Pathology Peking University Cancer Hospital and Institute Beijing ChinaDepartment of Nuclear Medicine State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration) Peking University Cancer Hospital & Institute Beijing ChinaDepartment of Nuclear Medicine State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration) Peking University Cancer Hospital & Institute Beijing ChinaDepartment of Nuclear Medicine State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration) Peking University Cancer Hospital & Institute Beijing ChinaMultitude Therapeutics Shanghai ChinaMultitude Therapeutics Shanghai ChinaMultitude Therapeutics Shanghai ChinaMultitude Therapeutics Shanghai ChinaDepartment of Renal Cancer and Melanoma Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital and Institute Beijing ChinaDepartment of Renal Cancer and Melanoma Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital and Institute Beijing ChinaDepartment of Renal Cancer and Melanoma Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital and Institute Beijing ChinaDepartment of Renal Cancer and Melanoma Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Peking University Cancer Hospital and Institute Beijing ChinaGuiZhou University Medical College Guiyang ChinaGuiZhou University Medical College Guiyang ChinaAbstract In the context of precision diagnosis for various subtypes of melanoma, identifying biomarkers with clinical translational potential from a molecular standpoint is crucial for a more comprehensive characterization of the disease. Mucin 18 (MUC18) is highly expressed in both tumor cells and tumor vasculature in major melanoma subtypes and is restricted to normal tissues. A noninvasive imaging approach for MUC18 in melanoma utilizing an immune positron emission tomography (PET) radionuclide‐conjugated drug (RDC) with an 89Zr‐labeled humanized anti‐MUC18 monoclonal antibody (mAb) was developed. A375, Sk‐Mel‐28, HMVII, and A549 cells and tumor model mice were conducted. Immuno‐PET was employed to assess the specificity and targeting of three distinct melanoma cell line‐derived xenografts (CDXs) and patient‐derived tumor xenografts (PDXs) in immunodeficient mice. The developed RDC, named 89Zr‐IP150, demonstrated robust in vitro stability and high binding affinity, ensuring reliable and specific PET imaging of small, medium, and large subcutaneous tumors in human melanoma mouse xenotransplantation models. Notably, for the first time, the clinical translational potential of 89Zr‐IP150 was successfully validated using PDX models. These findings present a noninvasive, real‐time method for the early screening of MUC18 (+) melanoma patients and are important for studying the early‐stage biological distribution of MUC18‐targeted antibody‐drug conjugates.https://doi.org/10.1002/VIW.20240055humanized mAbimmuno‐PET imagingmelanomaPDX model |
| spellingShingle | Qian Zhang Haizhen Du Xiuli Ma Song Liu Xiangxing Kong Muye Hu Jing Shi Yanfang Tang ShuHui Liu Xun Meng Qian Guo Yan Kong Jun Guo Bin Lian Zhi Yang Hua Zhu Mucin 18‐targeted humanized monoclonal antibody immune positron emission tomography imaging and patient‐derived tumor xenograft visualization View humanized mAb immuno‐PET imaging melanoma PDX model |
| title | Mucin 18‐targeted humanized monoclonal antibody immune positron emission tomography imaging and patient‐derived tumor xenograft visualization |
| title_full | Mucin 18‐targeted humanized monoclonal antibody immune positron emission tomography imaging and patient‐derived tumor xenograft visualization |
| title_fullStr | Mucin 18‐targeted humanized monoclonal antibody immune positron emission tomography imaging and patient‐derived tumor xenograft visualization |
| title_full_unstemmed | Mucin 18‐targeted humanized monoclonal antibody immune positron emission tomography imaging and patient‐derived tumor xenograft visualization |
| title_short | Mucin 18‐targeted humanized monoclonal antibody immune positron emission tomography imaging and patient‐derived tumor xenograft visualization |
| title_sort | mucin 18 targeted humanized monoclonal antibody immune positron emission tomography imaging and patient derived tumor xenograft visualization |
| topic | humanized mAb immuno‐PET imaging melanoma PDX model |
| url | https://doi.org/10.1002/VIW.20240055 |
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