TY - JOUR T1 - ImmunoPET of CD146 in breast cancer metastatic models JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1494 LP - 1494 VL - 62 IS - supplement 1 AU - Lei Kang AU - Cuicui Li AU - Carolina Ferreira AU - Jonathan Engle AU - Rongfu Wang AU - Dawei Jiang AU - Weibo Cai Y1 - 2021/05/01 UR - http://jnm.snmjournals.org/content/62/supplement_1/1494.abstract N2 - 1494Introduction: The overexpression of CD146 in breast cancer is considered a hallmark of tumor progression, metastasis, and poor outcome, particularly in triple negative breast cancer (TNBC). By imaging differential CD146 expressions in breast cancer, a noninvasive method for predictive prognosis and diagnosis was provided. This allowed for the development of a 64Cu-labeled CD146-specific monoclonal antibody (YY146), which was evaluated for its role in noninvasive imaging of CD146 expression within metastatic murine models of breast cancer. Methods: CD146 expression was screened in five human breast cancer cell lines (MDA-MB-435, ZR-75-30, SKBR3, MCF-7 and MDA-MB-231) using western blotting and cell immunofluorescent staining. Metastatic tumor murine models were then built with high or low levels of CD146 expression. YY146 was conjugated with 1,4,7-triazacyclononane-triacetic acid (NOTA) and radiolabeled with 64Cu following standard procedures. ImmunoPET and PET/CT imaging were used to evaluate in vivo and ex vivo uptake of 64Cu-NOTA-YY146 in lung metastatic xenograft tumor models at 4h, 12h, 24h and 48h in sequence. Finally, tissue immunofluorescent staining and hematoxylin and eosin (H&E) staining were performed on tumor tissues to verify imaging results. Results: Western blotting showed that the MDA-MB-435 cell line had the highest CD146 expression level whereas MCF-7 had the lowest level. Cell immunofluorescent staining confirmed high levels of YY146 expression in the MDA-MB-435 located on the cell membrane. The MDA-MB-435 and MCF-7 cell lines were used to build CD146-positive and -negative metastatic tumor models. The immunoPET imaging showed that the radioactive uptake of 64Cu-NOTA-YY146 in the heart, liver, and kidney gradually decreased over time. PET/CT results displayed that 64Cu-NOTA-YY146 allowed for the visualization of metastatic MDA-MB-435 tumors. The uptake of metastasis in lung metastatic xenograft tumor mice of MDA-MB-435 was higher than that of MCF-7 at 48 h post injection of 64Cu-NOTA-YY146, visualized by PET/CT imaging. Ex vivo biodistribution verified the PET imaging results. Radioactive uptake of the whole lung of MDA-MB-435 metastatic models was 7.06 ± 0.18 %ID/g, significantly higher than that of MCF-7 (2.17 ± 0.21 %ID/g). H&E staining and tissue immunofluorescent staining confirmed the expression level of CD146 in lung metastatic tumors. Conclusion: The tumor uptake of 64Cu-NOTA-YY146 showed positive correlation with CD146 expression levels in lung metastatic breast cancer models. 64Cu-NOTA-YY146 may be used as an immunoPET probe to visualize CD146 and potentially used for diagnosis, prognosis prediction and monitoring therapeutic response in breast cancer. Acknowledgements: This work was supported by the University of Wisconsin - Madison, the National Institutes of Health (P30CA014520), the National Natural Science Foundation of China (81871385), PKU medicine-X Youth Program (PKU2020LCXQ007) and Open Funding Project of the State Key Laboratory of Biochemical Engineering (2020KF-01). ER -