ImmunoPET of the differential expression of CD146 in breast cancer
Authors: Cuicui Li
Dawei Jiang
Yunan Yang
Weibo Cai
Anyanee Kamkaew
Lei Kang
Kendall E Barrett
Carolina A Ferreira
Jonathan W Engle
Eduardo Aluicio-Sarduy
Journal: American journal of cancer research (2021)
Discipline: CLINICAL MEDICINE
Keywords: 52Mn; 89Zr; CD146; ImmunoPET; YY146
Affiliations: Department of Biomedical Engineering, University of Wisconsin-Madison Madison, WI, USA., Department of Nuclear Medicine, Peking University First Hospital Beijing, China., Department of Radiology and Medical Physics, University of Wisconsin-Madison WI, USA., Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.

Abstract:  With advancement in antibody engineering, the development and characterization of new cancer-specific molecular targets are in the forefront of this PET-antibody combination "revolution". Overexpression of CD146 in different types of tumors, including breast tumor, has been associated with tumor progression and poor prognosis. Non-invasive detection of CD146 with a monoclonal antibody may provide a noninvasive diagnostic tool with high specificity and accountability. Methods: Herein, we have developed a CD146-specific monoclonal antibody (YY146), radiolabeled it with 52Mn and 89Zr and identified its capability in acting as a non-invasive imaging agent that specific targets CD146 in different murine breast cancer models. CD146 expression was first screened in different breast tumor cell lines through Western Blot and confirmed its binding ability to YY146 using Flow Cytometry. Serial immunoPET images were carried out after intravenous administration of 52Mn or 89Zr labeled YY146. In addition, we also performed in vivo fluorescence imaging in animals injected with YY146 conjugated with Cy5.5. Results: Western Blot results show that MDA-MB-435 cell line had greater levels of CD146 expression when compared to the other cell lines investigated. Flow cytometry confirmed binding ability of YY146. PET images revealed well correlated uptake between tumor uptake and CD146 expression levels, confirmed by biodistribution studies and fluorescence imaging. Conclusion: PET imaging, for up to 7 days, of mice bearing three different breast tumors were carried out and revealed radiotracer uptake in tumors that strongly (r2 = 0.98, P &lt; 0.01), correlated with CD146 expression levels, as confirmed by in vitro and ex vivo studies. 

Retracted: No

PubPeer comments:
 This papers makes use of * Four human breast cancer cell lines including MDA-MB-231 (HTB26), SKBR-3 (HTB30), MCF-7 (HTB22) and MDA-MB-435 (HTB-129) were used (ATCC; Manassas, VA, USA) * Unfortunatly one of these 4 cell lines, MDA-MB-435, is not a breast cancer cell line but is a M14 contaminated melanoma cell line. This was first shown in 2007: https: pubmed.ncbi.nlm.nih.gov 17004106 and in 2015 it was shown that unfortunatly many groups were still using it wrongly as a breast cancer cell line: https: www.nature.com articles npjbcancer20152 Finally in 2017 the definitive proof that M14 from which MDA-MB-435 derives is a melanoma cell lines was published: https: pubmed.ncbi.nlm.nih.gov 28940260 While the paper makes use of 3 other bona fide breast cancer cell lines, a number of observations and conclusions are invalidated by the incorrect use of MDA-MB-435 which was used specifically in the following context: * In order to evaluate if our tracer could differentiate and accumulate differently in tumor tissue according to CD146 expression, we have selected MDA-MB-435 cell line as our high-expression cell line * See the relevant [Cellosaurus entry] ,