Detection And Differentiation Of Breast Cancer Sub-Types Using A Cpla2 Alpha Activatable Fluorophore

Cytosolic phospholipase A2 alpha (cPLA2 alpha) has been shown to be elevated in breast cancer and is a potential biomarker in the differentiation of molecular sub-types. Using a cPLA2 alpha activatable fluorophore, DDAO arachidonate, we explore its ability to function as a contrast agent in fluorescence-guided surgery. In cell lines ranging in cPLA2 alpha expression and representing varying breast cancer sub-types, we show DDAO arachidonate activates with a high correlation to cPLA2 alpha expression level. Using a control probe, DDAO palmitate, in addition to cPLA2 alpha inhibition and genetic knockdown, we show that this activation is a result of cPLA2 alpha activity. In mouse models, using an ex vivo tumor painting technique, we show that DDAO arachidonate activates to a high degree in basal-like versus luminal-like breast tumors and healthy mammary tissue. Finally, we show that using an in vivo model, orthotopic basal-like tumors give significantly high probe activation compared to healthy mammary fat pads and surrounding tissue. Together we conclude that cPLA2 alpha activatable fluorophores such as DDAO arachidonate may serve as a useful contrast agent for the visualization of tumor margins in the fluorescence-guided surgery of basal-like breast cancer.