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.
背景/目的：胰腺导管腺癌（PDAC）在诊断时约50%的病例已处于晚期并伴有远处转移，预后极差。采用标准疗法治疗这种极具侵袭性的疾病仅能略微改善患者总生存期，这主要归因于缺乏针对性的早期治疗手段，而早期检测目前仍难以实现。黏蛋白-16（MUC16）作为一种糖蛋白，在超过60%的PDAC患者中过度表达，是肿瘤特异性生物标志物。 方法：本研究通过将靶向MUC16的人源化抗体（huAR9.6）与钆结合，开发了一种用于促进PDAC早期和晚期病变检测的磁共振成像（MRI）探针。 结果：在临床前小鼠模型中，这种靶向MUC16的MRI探针在皮下模型中能有效增强PDAC早期病变的对比度，并在原位模型中实现了对晚期胰腺癌肿瘤的检测。在给药剂量下，该探针未对重要器官产生任何毒性。 结论：本研究证实合成靶向MUC16的MRI探针具有可行性，能够对MUC16阳性PDAC病变实现更优的高分辨率对比增强，有助于病变检测并可能促成更佳的治疗策略。
肿瘤(癌症)患者之家