Simple Summary: Distinguishing pancreatic cancer from healthy tissue before and during surgery can be enhanced by using molecular tracers directed at molecules on tumor cells allowing high-contrast... Show moreSimple Summary: Distinguishing pancreatic cancer from healthy tissue before and during surgery can be enhanced by using molecular tracers directed at molecules on tumor cells allowing high-contrast visualization of tumor tissue, eventually improving diagnosis and surgical removal. Albeit sugar molecules and proteins carrying a large amount of sugars-mucins- have gained significant interest as tumor-specific targets, their relative presence on structures surrounding tumor tissues and lymph node metastases is unknown. The current study shows that the presence of several, but not all, investigated sugar molecules and mucins on pancreatic cancer cells is higher compared to surrounding tissues. Moreover, given their abundance on tumor cells in lymph nodes and their absence on normal lymph nodes, all investigated targets are high-potential targets for visualization of lymph node metastases. This study paves the way for the development of molecular tracers against the targets evaluated herein to allow improvement of pancreatic cancer treatment.Targeted molecular imaging may overcome current challenges in the preoperative and intraoperative delineation of pancreatic ductal adenocarcinoma (PDAC). Tumor-associated glycans Le(a/c/x), sdi-Le(a), sLe(a), sLe(x), 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(a/c/x), 94% for sdi-Le(a), 98% for sLe(a), 90% for sLe(x), 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, p < 0.0001) and healthy pancreatic tissues (MUC1 tumor:pancreas ratio: 1.0, p > 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(a/c/x)-, sdi-Le(a)-, sLe(a)-, sLe(x)- and MUC5AC-specific tracers for molecular imaging of PDAC imaging and their subsequent introduction into the clinic. Show less
Houvast, R.D.; Vankemmelbeke, M.; Durrant, L.G.; Wuhrer, M.; Baart, V.M.; Kuppen, P.J.K.; ... ; Sier, C.E.M. 2020
Simple SummaryDistinguishing malignancy from healthy tissue is essential for oncologic surgery. Targeted imaging during an operation aids the surgeon to operate better. The present tracers for... Show moreSimple SummaryDistinguishing malignancy from healthy tissue is essential for oncologic surgery. Targeted imaging during an operation aids the surgeon to operate better. The present tracers for detecting cancer are directed against proteins that are overexpressed on the membrane of tumor cells. This review evaluates the use of tumor-associated sugar molecules as an alternative for proteins to image cancer tissue. These sugar molecules are present as glycans on glycosylated membrane proteins and glycolipids. Due to their location and large numbers per cell, these sugar molecules might be better targets for tumor imaging than proteins.Real-time tumor imaging techniques are increasingly used in oncological surgery, but still need to be supplemented with novel targeted tracers, providing specific tumor tissue detection based on intra-tumoral processes or protein expression. To maximize tumor/non-tumor contrast, targets should be highly and homogenously expressed on tumor tissue only, preferably from the earliest developmental stage onward. Unfortunately, most evaluated tumor-associated proteins appear not to meet all of these criteria. Thus, the quest for ideal targets continues. Aberrant glycosylation of proteins and lipids is a fundamental hallmark of almost all cancer types and contributes to tumor progression. Additionally, overexpression of glycoproteins that carry aberrant glycans, such as mucins and proteoglycans, is observed. Selected tumor-associated glyco-antigens are abundantly expressed and could, thus, be ideal candidates for targeted tumor imaging. Nevertheless, glycan-based tumor imaging is still in its infancy. In this review, we highlight the potential of glycans, and heavily glycosylated proteoglycans and mucins as targets for multimodal tumor imaging by discussing the preclinical and clinical accomplishments within this field. Additionally, we describe the major advantages and limitations of targeting glycans compared to cancer-associated proteins. Lastly, by providing a brief overview of the most attractive tumor-associated glycans and glycosylated proteins in association with their respective tumor types, we set out the way for implementing glycan-based imaging in a clinical practice. Show less
Conclusions: Circulating TF(+)MPs and mucins may concertedly aggravate coagulopathy in PAC. Understanding of underlying mechanisms may result in new treatment strategies for VTE prevention and... Show moreConclusions: Circulating TF(+)MPs and mucins may concertedly aggravate coagulopathy in PAC. Understanding of underlying mechanisms may result in new treatment strategies for VTE prevention and improvement of survival. Show less
