ImmunoPET of the differential expression of CD146 in breast cancer

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.

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.

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.

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 < 0.01), correlated with CD146 expression levels, as confirmed by in vitro and ex vivo studies.