Exploiting the MUC5AC Antigen for Noninvasive Identification of Pancreatic Cancer
| Autor: | Susanne Klein-Scory, Marguerite Clyne, Travis M. Shaffer, Kelly E. Henry, Colm J. Reid, Jan Grimm, Holger Kalthoff, Wolff Schmiegel, Jason S. Lewis, Janine Ring, Thilo Bracht, Anuja Ogirala, Barbara Sitek, Christina Eilert-Micus, Kyeara N. Mack, Bence Sipos |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pathology
medicine.medical_specialty PET-CT CA-19-9 Antigen medicine.diagnostic_test biology business.industry Pancreatic Intraepithelial Neoplasia medicine.disease Immunohistochemistry Basic Science Investigation Pancreatic Neoplasms Antigen Pancreatic cancer Biopsy Biomarkers Tumor medicine biology.protein Pancreatitis Radiology Nuclear Medicine and imaging Antibody business |
| Zdroj: | J Nucl Med |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.120.256776 |
| Popis: | Pancreatic cancer (PC) remains the fourth leading cause of cancer death; therefore, there is a clinically unmet need for novel therapeutics and diagnostic markers to treat this devastating disease. Physicians often rely on biopsy or CT for diagnosis, but more specific protein biomarkers are highly desired to assess the stage and severity of PC in a noninvasive manner. Serum biomarkers such as carbohydrate antigen 19-9 are of particular interest as they are commonly elevated in PC but have exhibited suboptimal performance in the clinic. MUC5AC has emerged as a useful serum biomarker that is specific for PC versus inflammation. We developed RA96, an anti-MUC5AC antibody, to gauge its utility in PC diagnosis through immunohistochemical analysis and whole-body PET in PC. Methods: In this study, extensive biochemical characterization determined MUC5AC as the antigen for RA96. We then determined the utility of RA96 for MUC5AC immunohistochemistry on clinical PC and preclinical PC. Finally, we radiolabeled RA96 with (89)Zr to assess its application as a whole-body PET radiotracer for MUC5AC quantification in PC. Results: Immunohistochemical staining with RA96 distinguished chronic pancreatitis, pancreatic intraepithelial neoplasia, and varying grades of pancreatic ductal adenocarcinoma in clinical samples. (89)Zr-desferrioxamine-RA96 was able to detect MUC5AC with high specificity in mice bearing capan-2 xenografts. Conclusion: Our study demonstrated that RA96 can differentiate between inflammation and PC, improving the fidelity of PC diagnosis. Our immuno-PET tracer (89)Zr-desferrioxamine-RA96 shows specific detection of MUC5AC-positive tumors in vivo, highlighting the utility of MUC5AC targeting for diagnosis of PC. |
| Databáze: | OpenAIRE |
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