Jayasindu Mathiyazhagan, Christabelle Rajesh, Satish Sagar, Thomas C Caffrey, Ying Huang, Aaron M Mohs, Benjamin J Swanson, Michael A Hollingsworth, Cory L Brooks, Prakash Radhakrishnan
{"title":"Humanized Anti-MUC16 Antibody-Conjugated Contrast Agents for Magnetic Resonance Imaging of Pancreatic Cancer.","authors":"Jayasindu Mathiyazhagan, Christabelle Rajesh, Satish Sagar, Thomas C Caffrey, Ying Huang, Aaron M Mohs, Benjamin J Swanson, Michael A Hollingsworth, Cory L Brooks, Prakash Radhakrishnan","doi":"10.3390/cancers17060957","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background/Objectives:</b> Pancreatic ductal adenocarcinoma (PDAC) is diagnosed at a late stage with distant metastasis in an overwhelming 50% of cases, and the prognosis is poor. Treating this extremely aggressive disease with standard-of-care therapies has led to modest benefits in overall survival, mainly due to a lack of targeted early treatment modalities, as early detection has not yet been possible. Mucin-16 (MUC16) is a glycoprotein overexpressed in more than 60% of patients with PDAC and is a tumor-specific biomarker. <b>Methods:</b> In this study, a magnetic resonance imaging (MRI) probe to facilitate the detection of early and late lesions of PDAC is developed by conjugating a MUC16-targeted humanized antibody (huAR9.6) with gadolinium. <b>Results:</b> In preclinical mouse models, this MUC16-targeted MRI probe demonstrates effective contrast enhancement in early lesions of PDAC in the subcutaneous setting and allows for the detection of late-stage pancreatic cancer tumors in an orthotopic model. The probe did not induce any toxicity in vital organs at the administered doses. <b>Conclusions:</b> This study establishes that synthesizing a MUC16-targeted MRI probe is feasible and allows for the better high-resolution contrast enhancement of MUC16+ PDAC lesions to facilitate detection and possibly better treatment strategies.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 6","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940418/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancers","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/cancers17060957","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is diagnosed at a late stage with distant metastasis in an overwhelming 50% of cases, and the prognosis is poor. Treating this extremely aggressive disease with standard-of-care therapies has led to modest benefits in overall survival, mainly due to a lack of targeted early treatment modalities, as early detection has not yet been possible. Mucin-16 (MUC16) is a glycoprotein overexpressed in more than 60% of patients with PDAC and is a tumor-specific biomarker. Methods: In this study, a magnetic resonance imaging (MRI) probe to facilitate the detection of early and late lesions of PDAC is developed by conjugating a MUC16-targeted humanized antibody (huAR9.6) with gadolinium. Results: In preclinical mouse models, this MUC16-targeted MRI probe demonstrates effective contrast enhancement in early lesions of PDAC in the subcutaneous setting and allows for the detection of late-stage pancreatic cancer tumors in an orthotopic model. The probe did not induce any toxicity in vital organs at the administered doses. Conclusions: This study establishes that synthesizing a MUC16-targeted MRI probe is feasible and allows for the better high-resolution contrast enhancement of MUC16+ PDAC lesions to facilitate detection and possibly better treatment strategies.
期刊介绍:
Cancers (ISSN 2072-6694) is an international, peer-reviewed open access journal on oncology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.