ImmunoPET of CD146 in Orthotopic and Metastatic Breast Cancer Models
Authors: Xiaojie Xu
Rongfu Wang
Cuicui Li
Kaelyn V Becker
Yunan Yang
Dawei Jiang
Weibo Cai
Lei Kang
Kevin Fan
Hanxiao Liu
Nan Huo
Carolina A Ferreira
Jonathan W Engle
Journal: Bioconjugate chemistry (2021)
Discipline: CHEMISTRY
Keywords: CD146; breast cancer; immunoPET; prognosis; diagnosis
Affiliations: Department of Nuclear Medicine, Peking University First Hospital, Beijing, China 100034., Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States., Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States., Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China 100850., Department of Oncology, Harbin Medical University Affiliated Cancer Hospital, Harbin, China 150081., Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 430022.

Abstract:  The overexpression of CD146 in breast cancer is considered a hallmark of tumor progression and metastasis, particularly in triple negative breast cancer. Aimed at imaging differential CD146 expressions in breast cancer, a noninvasive method for predictive prognosis and diagnosis was investigated using a 64Cu-labeled CD146-specific monoclonal antibody, YY146. CD146 expression was screened in human breast cancer cell lines using Western blotting. Binding ability was evaluated using flow cytometry and immunofluorescent staining. YY146 was conjugated with 1,4,7-triazacyclononane-triacetic acid (NOTA) and radiolabeled with 64Cu following standard procedures. Serial PET or PET/CT imaging was performed in orthotopic and metastatic breast cancer tumor models. Biodistribution was performed after the final time point of imaging. Finally, tissue immunofluorescent staining and hematoxylin and eosin (H&amp;E) staining were performed on tumor tissues. The MDA-MB-435 cell line showed the highest CD146 expression level, whereas MCF-7 had the lowest level at the cellular level. ImmunoPET showed that MDA-MB-435 orthotopic tumors had high and clear radioactive accumulation after the administration of 64Cu-NOTA-YY146. The tumor uptake of 64Cu-NOTA-YY146 in MDA-MB-435 was significantly higher than that in MCF-7 and nonspecific IgG control groups (P &lt; 0.01). Biodistribution verified the PET imaging results. For metastatic models, 64Cu-NOTA-YY146 allowed for the visualization of high radioactivity accumulation in metastatic MDA-MB-435 tumors, which was confirmed by ex vivo biodistribution of lung tissues. H&amp;E staining proved the successful building of metastatic tumor models. Immunofluorescent staining verified the differential expression of CD146 in orthotopic tumors. Therefore, 64Cu-NOTA-YY146 could be used as an immunoPET probe to visualize CD146 in the breast cancer model and is potentially useful for cancer diagnosis, prognosis prediction, and monitoring therapeutic response. 

Retracted: No

PubPeer comments:
 Figure 9 appears to have two images of stomach tissue which overlap (XLGB-H and XLGB-M). *** Enhanced contrast ![file] *** ![file] , 
 November 9, 2020  In the original article, there was an error in Figure 9. An image of the high-dose group was inserted into the middle-dose group in the stomach row. The correct Figure 9 appears below. ![file]  The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. ,