Near-Infrared Imaging of Colonic Adenomas In Vivo Using Orthotopic Human Organoids for Early Cancer Detection
Colorectal cancer is a leading cause of cancer-related morbidity and mortality worldwide. Premalignant lesions that are flat and subtle in morphology are often missed in conventional colonoscopies. Patient-derived adenoma colonoids with high and low cMet expression and normal colonoids were implante...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/19/4795 |
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| author | Xiaoli Wu Chun-Wei Chen Sangeeta Jaiswal Tse-Shao Chang Ruoliu Zhang Michael K. Dame Yuting Duan Hui Jiang Jason R. Spence Sen-Yung Hsieh Thomas D. Wang |
| author_facet | Xiaoli Wu Chun-Wei Chen Sangeeta Jaiswal Tse-Shao Chang Ruoliu Zhang Michael K. Dame Yuting Duan Hui Jiang Jason R. Spence Sen-Yung Hsieh Thomas D. Wang |
| author_sort | Xiaoli Wu |
| collection | DOAJ |
| description | Colorectal cancer is a leading cause of cancer-related morbidity and mortality worldwide. Premalignant lesions that are flat and subtle in morphology are often missed in conventional colonoscopies. Patient-derived adenoma colonoids with high and low cMet expression and normal colonoids were implanted orthotopically in the colon of immunocompromised mice to serve as a preclinical model system. A peptide specific for cMet was labeled with IRDye800, a near-infrared (NIR) fluorophore. This peptide was administered intravenously, and in vivo imaging was performed using a small animal fluorescence endoscope. Quantified intensities showed a peak target-to-background ratio at ~1 h after intravenous peptide injection, and the signal cleared by ~24 h. The peptide was stable in serum with a half-life of 3.6 h. Co-staining of adenoma and normal colonoids showed a high correlation between peptide and anti-cMet antibody. A human-specific cytokeratin stain verified the presence of human tissues implanted among surrounding normal mouse colonic mucosa. Peptide biodistribution was consistent with rapid renal clearance. No signs of acute toxicity were found on either animal necropsy or serum hematology and chemistries. Human colonoids provide a clinically relevant preclinical model to evaluate the specific uptake of a NIR peptide to detect premalignant colonic lesions in vivo. |
| first_indexed | 2024-03-10T21:47:51Z |
| format | Article |
| id | doaj.art-a505608a8a824d53adc17fac7209fe7c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T21:47:51Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a505608a8a824d53adc17fac7209fe7c2023-11-19T14:10:40ZengMDPI AGCancers2072-66942023-09-011519479510.3390/cancers15194795Near-Infrared Imaging of Colonic Adenomas In Vivo Using Orthotopic Human Organoids for Early Cancer DetectionXiaoli Wu0Chun-Wei Chen1Sangeeta Jaiswal2Tse-Shao Chang3Ruoliu Zhang4Michael K. Dame5Yuting Duan6Hui Jiang7Jason R. Spence8Sen-Yung Hsieh9Thomas D. Wang10Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USADivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USADivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, TaiwanDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USAColorectal cancer is a leading cause of cancer-related morbidity and mortality worldwide. Premalignant lesions that are flat and subtle in morphology are often missed in conventional colonoscopies. Patient-derived adenoma colonoids with high and low cMet expression and normal colonoids were implanted orthotopically in the colon of immunocompromised mice to serve as a preclinical model system. A peptide specific for cMet was labeled with IRDye800, a near-infrared (NIR) fluorophore. This peptide was administered intravenously, and in vivo imaging was performed using a small animal fluorescence endoscope. Quantified intensities showed a peak target-to-background ratio at ~1 h after intravenous peptide injection, and the signal cleared by ~24 h. The peptide was stable in serum with a half-life of 3.6 h. Co-staining of adenoma and normal colonoids showed a high correlation between peptide and anti-cMet antibody. A human-specific cytokeratin stain verified the presence of human tissues implanted among surrounding normal mouse colonic mucosa. Peptide biodistribution was consistent with rapid renal clearance. No signs of acute toxicity were found on either animal necropsy or serum hematology and chemistries. Human colonoids provide a clinically relevant preclinical model to evaluate the specific uptake of a NIR peptide to detect premalignant colonic lesions in vivo.https://www.mdpi.com/2072-6694/15/19/4795imagingcancerearly detectioncMetpeptidefluorescence |
| spellingShingle | Xiaoli Wu Chun-Wei Chen Sangeeta Jaiswal Tse-Shao Chang Ruoliu Zhang Michael K. Dame Yuting Duan Hui Jiang Jason R. Spence Sen-Yung Hsieh Thomas D. Wang Near-Infrared Imaging of Colonic Adenomas In Vivo Using Orthotopic Human Organoids for Early Cancer Detection Cancers imaging cancer early detection cMet peptide fluorescence |
| title | Near-Infrared Imaging of Colonic Adenomas In Vivo Using Orthotopic Human Organoids for Early Cancer Detection |
| title_full | Near-Infrared Imaging of Colonic Adenomas In Vivo Using Orthotopic Human Organoids for Early Cancer Detection |
| title_fullStr | Near-Infrared Imaging of Colonic Adenomas In Vivo Using Orthotopic Human Organoids for Early Cancer Detection |
| title_full_unstemmed | Near-Infrared Imaging of Colonic Adenomas In Vivo Using Orthotopic Human Organoids for Early Cancer Detection |
| title_short | Near-Infrared Imaging of Colonic Adenomas In Vivo Using Orthotopic Human Organoids for Early Cancer Detection |
| title_sort | near infrared imaging of colonic adenomas in vivo using orthotopic human organoids for early cancer detection |
| topic | imaging cancer early detection cMet peptide fluorescence |
| url | https://www.mdpi.com/2072-6694/15/19/4795 |
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