Houvast Ruben D, Thijse Kira, Groen Jesse V, Chua JiaXin, Vankemmelbeke Mireille, Durrant Lindy G, Mieog J Sven D, Bonsing Bert A, Vahrmeijer Alexander L, Kuppen Peter J K, Crobach A Stijn L P, Sier Cornelis F M
Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK.
Cancers (Basel). 2021 Nov 18;13(22):5777. doi: 10.3390/cancers13225777.
Targeted molecular imaging may overcome current challenges in the preoperative and intraoperative delineation of pancreatic ductal adenocarcinoma (PDAC). Tumor-associated glycans Le, sdi-Le, sLe, sLe, sTn as well as mucin-1 (MUC1) and mucin-5AC (MU5AC) have gained significant interest as targets for PDAC imaging. To evaluate their PDAC molecular imaging potential, biomarker expression was determined using immunohistochemistry on PDAC, (surrounding) chronic pancreatitis (CP), healthy pancreatic, duodenum, positive (LN) and negative lymph node (LN) tissues, and quantified using a semi-automated digital image analysis workflow. Positive expression on PDAC tissues was found on 83% for Le, 94% for sdi-Le, 98% for sLe, 90% for sLe, 88% for sTn, 96% for MUC1 and 67% for MUC5AC, where all were not affected by the application of neoadjuvant therapy. Compared to PDAC, all biomarkers were significantly lower expressed on CP, healthy pancreatic and duodenal tissues, except for sTn and MUC1, which showed a strong expression on duodenum (sTn tumor:duodenum ratio: 0.6, < 0.0001) and healthy pancreatic tissues (MUC1 tumor:pancreas ratio: 1.0, > 0.9999), respectively. All biomarkers are suitable targets for correct identification of LN, as well as the distinction of LN from LN tissues. To conclude, this study paves the way for the development and evaluation of Le-, sdi-Le-, sLe-, sLe- and MUC5AC-specific tracers for molecular imaging of PDAC imaging and their subsequent introduction into the clinic.
靶向分子成像可能会克服目前在术前和术中对胰腺导管腺癌（PDAC）进行界定方面所面临的挑战。肿瘤相关聚糖Le、唾液酸化Le、唾液酸化Le、唾液酸化Le、sTn以及粘蛋白-1（MUC1）和粘蛋白-5AC（MU5AC）作为PDAC成像的靶点已引起了极大关注。为了评估它们在PDAC分子成像方面的潜力，采用免疫组织化学方法在PDAC、（周围）慢性胰腺炎（CP）、健康胰腺、十二指肠、阳性（LN）和阴性淋巴结（LN）组织中测定生物标志物的表达，并使用半自动数字图像分析工作流程进行定量分析。在PDAC组织上，Le的阳性表达率为83%，唾液酸化Le为94%，唾液酸化Le为98%，唾液酸化Le为90%，sTn为88%，MUC1为96%，MUC5AC为67%，所有这些均不受新辅助治疗应用的影响。与PDAC相比，除sTn和MUC1外，所有生物标志物在CP、健康胰腺和十二指肠组织中的表达均显著降低，其中sTn在十二指肠（sTn肿瘤：十二指肠比值：0.6，<0.0001）和健康胰腺组织（MUC1肿瘤：胰腺比值：1.0，>0.9999）上分别显示出强表达。所有生物标志物都是正确识别LN以及区分LN与LN组织的合适靶点。总之，本研究为开发和评估用于PDAC成像分子成像的Le、唾液酸化Le、唾液酸化Le、唾液酸化Le和MUC5AC特异性示踪剂及其随后引入临床铺平了道路。
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