Novel Imaging Strategy Detects Multiple Sub-Types of Triple-Negative Breast Cancer

A newly developed molecular imaging technique can identify multiple subtypes of triple-negative breast cancer (TNBC), enabling earlier and more accurate detection of this aggressive disease, according to new research published in the June issue of The Journal of Nuclear Medicine. 

TNBC is a heterogeneous disease, meaning it encompasses a wide range of different subtypes with varying biological behaviors and clinical outcomes. This makes it harder to identify, and as a result, TNBC lags behind other breast cancer types in targeted therapeutic and diagnostic imaging agent development. To address this challenge, researchers developed an imaging agent that could detect multiple TNBC subtypes and improve diagnostic capacity.

The research team targeted extra domain A of fibronectin (EDA-FN), a stable protein in the tumor stromal environment abundantly expressed in breast cancer. They created a monoclonal antibody-based PET tracer, [^89Zr]Zr-DFO-F8, to detect EDA-FN. This tracer was evaluated in vitro and in vivo in several preclinical xenograft models of multiple TNBC subtypes. [^89Zr]Zr-DFO-F8 exhibited specific, blockable EDA-FN binding activity in vitro. In vivo experiments demonstrated high tumor uptake in preclinical TNBC xenograft models. [^89Zr]Zr-DFO-F8 also detected EDA-FN in subcutaneous and orthotopic TNBC xenografts and accumulated in aggressive disease concordantly with EDA-FN expression. 

“These findings highlight the potential of targeting extracellular matrix proteins to overcome tumor heterogeneity in imaging, offering improved diagnostic and therapeutic potential,” noted Jason Lewis, PhD, Emily Tow Chair at Memorial Sloan Kettering Cancer Center. “This approach paves the way for more universal, tumor microenvironment-based tracers in nuclear medicine and could expand precision imaging across diverse and hard-to-target cancers.” 

The study, titled “Targeting Extra Domain A of Fibronectin to Improve Noninvasive Detection of Triple-Negative Breast Cancer,” was conducted by researchers from Memorial Sloan Kettering Cancer Center, Weill Cornell Graduate School of Medical Sciences, and Philochem AG.