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MUC18-targeted humanized monoclonal antibody immunePET imaging and patient-derived tumor xenograft visualization
  • +13
  • 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
Qian Zhang
Peking University Cancer Hospital
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Haizhen Du
Peking University Cancer Hospital
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Xiuli Ma
Peking University Cancer Hospital
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Song Liu
Peking University Cancer Hospital
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Xiangxing Kong
Peking University Cancer Hospital
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Muye Hu
Peking University Cancer Hospital
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Jing Shi
Multitude Therapeutics
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Yanfang Tang
Multitude Therapeutics
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Shuhui Liu
Multitude Therapeutics
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Xun Meng
Multitude Therapeutics
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Qian Guo
Peking University Cancer Hospital
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Yan Kong
Peking University Cancer Hospital
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Jun Guo
Peking University Cancer Hospital
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Bin Lian
Peking University Cancer Hospital
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Zhi Yang
Peking University Cancer Hospital
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Hua Zhu
Peking University Cancer Hospital

Corresponding Author:[email protected]

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Abstract

Background: 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. MUC18 is highly expressed in both tumor cells and tumor vasculature in major melanoma subtypes and is restricted to normal tissues. Methods: 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. Results: 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 a PDX model. Conclusions: 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 (ADCs).
30 Jun 2024Submitted to View
18 Jul 2024Submission Checks Completed
18 Jul 2024Assigned to Editor
18 Jul 2024Review(s) Completed, Editorial Evaluation Pending
18 Jul 2024Reviewer(s) Assigned
13 Aug 2024Editorial Decision: Revise Major
28 Sep 20241st Revision Received
28 Sep 2024Submission Checks Completed
28 Sep 2024Assigned to Editor
28 Sep 2024Review(s) Completed, Editorial Evaluation Pending
29 Sep 2024Reviewer(s) Assigned
24 Oct 2024Editorial Decision: Accept