cancers Article The Expression Proﬁle and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy Ashleigh Hull 1, * , Yanrui Li 1 , Dylan Bartholomeusz 2,3 , William Hsieh 1,2 , Samantha Escarbe 4 , Andrew Ruszkiewicz 4,5 and Eva Bezak 1,6   Citation: Hull, A.; Li, Y.; Bartholomeusz, D.; Hsieh, W.; Escarbe, S.; Ruszkiewicz, A.; Bezak, E. The Expression Proﬁle and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy. Cancers 2021, 13, 61. https://doi.org/10.3390/ cancers13010061 Received: 3 November 2020 Accepted: 22 December 2020 Published: 28 December 2020 Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional claims in published maps and institutional afﬁliations. Copyright: © 2020 by the authors. Li- censee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/). 1 Cancer Research Institute and Allied Health and Human Performance Academic Unit, University of South Australia, Adelaide, SA 5000, Australia; judy.li@unisa.edu.au (Y.L.); william.hsieh@sa.gov.au (W.H.); eva.bezak@unisa.edu.au (E.B.) 2 Department of PET, Nuclear Medicine & Bone Densitometry, SA Medical Imaging, Royal Adelaide Hospital, Adelaide, SA 5000, Australia; dylan.bartholomeusz@sa.gov.au 3 Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia 4 Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia; samantha.escarbe@sa.gov.au (S.E.); andrew.ruszkiewicz@sa.gov.au (A.R.) 5 Division of Anatomical Pathology, SA Pathology, Adelaide, SA 5000, Australia 6 Department of Physics, The University of Adelaide, Adelaide, SA 5000, Australia * Correspondence: ashleigh.hull@mymail.unisa.edu.au Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is a cancer of low survival needing novel treatment approaches such as targeted therapies. If a target is overexpressed on PDAC cells but has minimal expression on normal cells, it is considered a good candidate for targeted therapy. Identifying targets with this expression pattern can help to optimise targeted therapies to be therapeutically effective without compromising on tolerability. The aim of this study was to assess the expression of the MUC1 receptor using the C595 antibody. We performed a series of cell line and tissue studies to identify if the expression of the MUC1 receptor changes between different pancreatic pathologies, including PDAC and normal pancreatic tissue. We found that the MUC1 receptor is both overexpressed and more uniformly expressed in PDAC compared to the other tissue types assessed. This indicates that the MUC1 receptor is a feasible target for targeted therapies of PDAC. Abstract: Improvements in the prognosis of pancreatic ductal adenocarcinoma (PDAC) rely on the development of effective treatments to target advanced disease. Mucin 1 (MUC1) is a transmembrane glycoprotein which is involved in the metastatic progression of PDAC and is a receptor-of-interest for targeted radionuclide therapy. The aim of this study was to determine the feasibility of MUC1-based targeted radionuclide therapy for PDAC, by evaluating the expression proﬁle of MUC1 in different pancreatic cells and tissues using the C595 antibody. MUC1 expression was evaluated in four PDAC cell lines (PANC-1, BxPC-3, CAPAN-1 and AsPC-1) using ﬂow cytometry and immunocytochemistry. Immunohistochemistry was performed on primary and metastatic PDAC, pancreatitis, pancreatic intra-epithelial neoplasia and normal pancreatic tissue samples to identify potential changes in C595- reactive MUC1 expression across different disease groups. C595-reactive MUC1 expression was found to varying degrees in the cell lines (11.5–93.1%). A pixel analysis of the immunohistochemical staining demonstrated highest MUC1 expression in primary PDAC tissue (mean pixel value of 205.4), followed by other pancreatic cancer types (204.9), pancreatic intra-epithelial neoplasia (203.8), metastatic PDAC (201.5), chronic pancreatitis (198.1) and normal pancreatic tissue (191.4). The increased expression in malignant tissues and reduced expression in benign tissues indicate that C595-reactive MUC1 is a potential target for targeted radionuclide therapy of PDAC. Keywords: pancreatic cancer; mucin 1; targeted radionuclide therapy; textural analysis Cancers 2021, 13, 61. https://doi.org/10.3390/cancers13010061 https://www.mdpi.com/journal/cancers