Humanized Anti-MUC16 Antibody-Conjugated Contrast Agents for Magnetic Resonance Imaging of Pancreatic Cancer.

IF 4.5 2区 医学 Q1 ONCOLOGY
Cancers Pub Date : 2025-03-12 DOI:10.3390/cancers17060957
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
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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.

人源抗muc16抗体偶联造影剂用于胰腺癌磁共振成像。
背景/目的:胰腺导管腺癌(Pancreatic ductal adenocarcinoma, PDAC)在晚期确诊并有远处转移的病例占压倒性的50%,预后较差。用标准治疗方法治疗这种极具侵袭性的疾病,在总体生存方面带来了适度的好处,这主要是由于缺乏有针对性的早期治疗方式,因为早期发现尚不可能。Mucin-16 (MUC16)是一种糖蛋白,在超过60%的PDAC患者中过表达,是一种肿瘤特异性生物标志物。方法:本研究通过偶联muc16靶向人源抗体(huAR9.6)与钆,研制了一种磁共振成像(MRI)探针,用于检测PDAC的早期和晚期病变。结果:在临床前小鼠模型中,这种muc16靶向MRI探针在皮下设置的PDAC早期病变中显示出有效的造影剂增强,并允许在原位模型中检测晚期胰腺癌肿瘤。在给药剂量下,探针不会对重要器官产生任何毒性。结论:本研究表明,合成MUC16靶向MRI探针是可行的,并且可以对MUC16+ PDAC病变进行更好的高分辨率对比度增强,从而促进检测,并可能提供更好的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancers
Cancers Medicine-Oncology
CiteScore
8.00
自引率
9.60%
发文量
5371
审稿时长
18.07 days
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.
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