National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan.
Nihon Medi-Physics Co., Ltd., Tokyo, 136-0075, Japan.
Sci Rep. 2020 Mar 10;10(1):4143. doi: 10.1038/s41598-020-61056-5.
Pancreatic cancer (PC) has a poor prognosis owing to difficulties in the diagnosis of resectable PC at early stages. Several clinical studies have indicated that the detection and surgery of small resectable PC (<1 cm) can significantly improve survival; however, imaging diagnosis and accurate resection of small PC remain challenging. Here, we report the feasibility of "immuno-OpenPET" as a novel approach enabling not only early diagnosis but also image-guided surgery, using a small (<1 cm) resectable PC orthotopic xenograft mouse model. For immuno-OpenPET, we utilized our original OpenPET system, which enables high-resolution positron emission tomography (PET) imaging with depth-of-interaction detectors, as well as real-time image-guided surgery, by arranging the detectors to create an open space for surgery and accelerating the image reconstruction process by graphics processing units. For immuno-OpenPET, Cu-labeled anti-epidermal growth factor receptor antibody cetuximab was intraperitoneally administered into mice. It clearly identified PC tumors ≥3 mm. In contrast, neither OpenPET with intravenous-administered Cu-cetuximab nor intraperitoneal/intravenous-administered F-FDG (a traditional PET probe) could detect PC in this model. Immuno-OpenPET-guided surgery accurately resected small PC in mice and achieved significantly prolonged survival. This technology could provide a novel diagnostic and therapeutic strategy for small resectable PC to improve patient survival.
由于在早期诊断可切除胰腺癌 (PC) 方面存在困难,PC 的预后较差。几项临床研究表明,检测和手术切除小的可切除 PC(<1cm)可以显著改善生存;然而,小 PC 的成像诊断和准确切除仍然具有挑战性。在这里,我们报告了“免疫 OpenPET”作为一种新方法的可行性,该方法不仅可以实现早期诊断,还可以使用小 (<1cm) 可切除 PC 原位异种移植小鼠模型进行图像引导手术。对于免疫 OpenPET,我们利用了我们原始的 OpenPET 系统,该系统利用具有相互作用深度探测器的高分辨率正电子发射断层扫描 (PET) 成像,以及通过安排探测器创建手术开放空间和通过图形处理单元加速图像重建过程的实时图像引导手术。对于免疫 OpenPET,将 Cu 标记的抗表皮生长因子受体抗体西妥昔单抗腹膜内给予小鼠。它可以清楚地识别≥3mm 的 PC 肿瘤。相比之下,静脉内给予 Cu-西妥昔单抗的 OpenPET 或腹膜内/静脉内给予 F-FDG(传统 PET 探针)都不能在该模型中检测到 PC。免疫 OpenPET 引导的手术准确切除了小鼠体内的小 PC,并显著延长了生存时间。这项技术可以为小的可切除 PC 提供一种新的诊断和治疗策略,以提高患者的生存率。