Glypican‐1 as a target for fluorescence molecular imaging of bladder cancer
Objectives To investigate whether anti‐glypican‐1 antibody Miltuximab conjugated with near‐infrared dye IRDye800CW can be used for in vivo fluorescence imaging of urothelial carcinoma. Methods The conjugate, Miltuximab‐IRDye800CW, was produced and characterized by size exclusion chromatography and f...
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Published in | International journal of urology Vol. 28; no. 12; pp. 1290 - 1297 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
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01.12.2021
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Abstract | Objectives
To investigate whether anti‐glypican‐1 antibody Miltuximab conjugated with near‐infrared dye IRDye800CW can be used for in vivo fluorescence imaging of urothelial carcinoma.
Methods
The conjugate, Miltuximab‐IRDye800CW, was produced and characterized by size exclusion chromatography and flow cytometry with glypican‐1‐expressing cells. Balb/c nude mice bearing subcutaneous urothelial carcinoma xenografts were intravenously injected with Miltuximab‐IRDye800CW or control IgG‐IRDye800CW and imaged daily by fluorescence imaging. After 10 days, tumors and major organs were collected for ex vivo study of the conjugate biodistribution, including its accumulation in the tumor.
Results
The intravenous injection of Miltuximab‐IRDye800CW to tumor‐bearing mice showed its specific accumulation in the tumors with the tumor‐to‐background ratio of 12.7 ± 2.4, which was significantly higher than that in the control group (4.6 ± 0.9, P < 0.005). The ex vivo imaging was consistent with the in vivo findings, with tumors from the mice injected with Miltuximab‐IRDye800CW being significantly brighter than the organs or the control tumors.
Conclusions
The highly specific accumulation and retention of Miltuximab‐IRDye800CW in glypican‐1‐expressing tumors in vivo shows its high potential for fluorescence imaging of urothelial carcinoma and warrants its further investigation toward clinical translation. |
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AbstractList | OBJECTIVESTo investigate whether anti-glypican-1 antibody Miltuximab conjugated with near-infrared dye IRDye800CW can be used for in vivo fluorescence imaging of urothelial carcinoma. METHODSThe conjugate, Miltuximab-IRDye800CW, was produced and characterized by size exclusion chromatography and flow cytometry with glypican-1-expressing cells. Balb/c nude mice bearing subcutaneous urothelial carcinoma xenografts were intravenously injected with Miltuximab-IRDye800CW or control IgG-IRDye800CW and imaged daily by fluorescence imaging. After 10 days, tumors and major organs were collected for ex vivo study of the conjugate biodistribution, including its accumulation in the tumor. RESULTSThe intravenous injection of Miltuximab-IRDye800CW to tumor-bearing mice showed its specific accumulation in the tumors with the tumor-to-background ratio of 12.7 ± 2.4, which was significantly higher than that in the control group (4.6 ± 0.9, P < 0.005). The ex vivo imaging was consistent with the in vivo findings, with tumors from the mice injected with Miltuximab-IRDye800CW being significantly brighter than the organs or the control tumors. CONCLUSIONSThe highly specific accumulation and retention of Miltuximab-IRDye800CW in glypican-1-expressing tumors in vivo shows its high potential for fluorescence imaging of urothelial carcinoma and warrants its further investigation toward clinical translation. Objectives To investigate whether anti‐glypican‐1 antibody Miltuximab conjugated with near‐infrared dye IRDye800CW can be used for in vivo fluorescence imaging of urothelial carcinoma. Methods The conjugate, Miltuximab‐IRDye800CW, was produced and characterized by size exclusion chromatography and flow cytometry with glypican‐1‐expressing cells. Balb/c nude mice bearing subcutaneous urothelial carcinoma xenografts were intravenously injected with Miltuximab‐IRDye800CW or control IgG‐IRDye800CW and imaged daily by fluorescence imaging. After 10 days, tumors and major organs were collected for ex vivo study of the conjugate biodistribution, including its accumulation in the tumor. Results The intravenous injection of Miltuximab‐IRDye800CW to tumor‐bearing mice showed its specific accumulation in the tumors with the tumor‐to‐background ratio of 12.7 ± 2.4, which was significantly higher than that in the control group (4.6 ± 0.9, P < 0.005). The ex vivo imaging was consistent with the in vivo findings, with tumors from the mice injected with Miltuximab‐IRDye800CW being significantly brighter than the organs or the control tumors. Conclusions The highly specific accumulation and retention of Miltuximab‐IRDye800CW in glypican‐1‐expressing tumors in vivo shows its high potential for fluorescence imaging of urothelial carcinoma and warrants its further investigation toward clinical translation. To investigate whether anti-glypican-1 antibody Miltuximab conjugated with near-infrared dye IRDye800CW can be used for in vivo fluorescence imaging of urothelial carcinoma. The conjugate, Miltuximab-IRDye800CW, was produced and characterized by size exclusion chromatography and flow cytometry with glypican-1-expressing cells. Balb/c nude mice bearing subcutaneous urothelial carcinoma xenografts were intravenously injected with Miltuximab-IRDye800CW or control IgG-IRDye800CW and imaged daily by fluorescence imaging. After 10 days, tumors and major organs were collected for ex vivo study of the conjugate biodistribution, including its accumulation in the tumor. The intravenous injection of Miltuximab-IRDye800CW to tumor-bearing mice showed its specific accumulation in the tumors with the tumor-to-background ratio of 12.7 ± 2.4, which was significantly higher than that in the control group (4.6 ± 0.9, P < 0.005). The ex vivo imaging was consistent with the in vivo findings, with tumors from the mice injected with Miltuximab-IRDye800CW being significantly brighter than the organs or the control tumors. The highly specific accumulation and retention of Miltuximab-IRDye800CW in glypican-1-expressing tumors in vivo shows its high potential for fluorescence imaging of urothelial carcinoma and warrants its further investigation toward clinical translation. |
Author | Lu, Yanling Campbell, Douglas H Wu, Angela Polikarpov, Dmitry M Lund, Maria E Walsh, Bradley J Gillatt, David A Zvyagin, Andrei V Palapattu, Ganesh S Zaslavsky, Alexander B |
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To investigate whether anti‐glypican‐1 antibody Miltuximab conjugated with near‐infrared dye IRDye800CW can be used for in vivo fluorescence imaging... To investigate whether anti-glypican-1 antibody Miltuximab conjugated with near-infrared dye IRDye800CW can be used for in vivo fluorescence imaging of... ObjectivesTo investigate whether anti‐glypican‐1 antibody Miltuximab conjugated with near‐infrared dye IRDye800CW can be used for in vivo fluorescence imaging... OBJECTIVESTo investigate whether anti-glypican-1 antibody Miltuximab conjugated with near-infrared dye IRDye800CW can be used for in vivo fluorescence imaging... |
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SubjectTerms | Animals Bladder cancer Cancer Carcinoma, Transitional Cell Cell Line, Tumor Flow cytometry Fluorescence fluorescence‐guided surgery Glypicans glypican‐1 Heparan sulfate proteoglycans Immunoglobulin G Intravenous administration Mice Mice, Nude Molecular Imaging monoclonal antibodies Optical Imaging Tissue Distribution Tumors urinary bladder neoplasms Urinary Bladder Neoplasms - diagnostic imaging Urothelial carcinoma Xenografts |
Title | Glypican‐1 as a target for fluorescence molecular imaging of bladder cancer |
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