Surgical resection is currently the only potentially curative option for patients with pancreatic cancer. However, the 5-year survival rate after resection is only 25%, due in part to high rates of R1 resections, in which cells are left behind at the surgical margin, resulting in disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to reduce incomplete resections and improve intraoperative assessment of cancer. Mucin-16 (MUC16), a protein biomarker highly overexpressed in pancreatic cancer, is a potential target for FGS. In this study, we developed a fluorescent MUC16-targeted antibody probe, AR9.6-IRDye800, for image-guided resection of pancreatic cancer. We demonstrated the efficacy of this probe to bind human pancreatic cancer cell lines in vitro and in vivo. In an orthotopic xenograft model, AR9.6-IRDye800 exhibited superior fluorescence enhancement of tumors and lower signal in critical background organs in comparison to a nonspecific IgG control. The results of this study suggest that AR9.6-IRDye800 has potential for success as a probe for FGS in pancreatic cancer patients, and MUC16 is a feasible target for intraoperative imaging.

中文翻译：

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开发用于胰腺癌术中成像的 MUC16 靶向近红外荧光抗体偶联物

手术切除是目前胰腺癌患者唯一可能治愈的选择。然而，切除后的 5 年生存率仅为 25%，部分原因是 R1 切除率较高，细胞残留在手术边缘，导致疾病复发。荧光引导手术（FGS）已成为减少不完全切除并改善癌症术中评估的一种方法。Mucin-16 (MUC16) 是一种在胰腺癌中高度过表达的蛋白质生物标志物，是 FGS 的潜在靶点。在这项研究中，我们开发了一种荧光MUC16靶向抗体探针AR9.6-IRDye800，用于图像引导胰腺癌切除术。我们证明了该探针在体外和体内结合人胰腺癌细胞系的功效。在原位异种移植模型中，与非特异性 IgG 对照相比，AR9.6-IRDye800 表现出出色的肿瘤荧光增强作用和关键背景器官中较低的信号。这项研究的结果表明，AR9.6-IRDye800 作为胰腺癌患者 FGS 探针具有成功的潜力，而 MUC16 是术中成像的可行靶点。