| Autor: |
Christine M. Nelson, Heather Knight, Jamie Erickson, Bradford L. McRae, Victor Sun, Annette J. Schwartz Sterman, Stephanie M. Gaudette, Grace Lynch, Kristoff T. Homan, Calvin S. Pohl, Sahana Bose, Liang Zhang, Soumya Mitra |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.21203/rs.3.rs-984872/v1 |
| Popis: |
Purpose To image colon-expressed alternatively spliced D domain of tenascin C in preclinical colitis models using near infrared (NIR) labeled targeted molecular imaging agents.Methods Human IgG and scFv fusion proteins specific to the alternatively spliced D domain of tenascin C were generated. Immunohistochemistry identified disease-specific expression of this extracellular matrix in mouse colitis models. Proteins were labeled with the NIR fluorophore IRDye 800CW via amine chemistry and intravenously dosed to evaluate targeting specificity in preclinical rodent and primate colitis models.Results The NIR labeled proteins successfully targeted colonic lesions in a murine model of colitis and appeared as distinct punctate spots. Co-administration of a blocking dose reduced the whole colon standardized uptake of the fluorescent dose >7-fold in mouse models. Estimates suggest local expression at >100 nM in diseased mouse colon. Macroscopic targeting specificity was not observed in diseased primate colon. Cellular level specificity was assessed via microscopy and immunohistochemistry.Conclusion Our imaging data suggest the alternatively spliced D domain of tenascin C is a promising target for delivery-based applications in inflammatory bowel diseases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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