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 a paper published in The Journal of Nuclear Medicine titled “Targeting Extra Domain A of Fibronectin to Improve Noninvasive Detection of Triple-Negative Breast Cancer.“

This approach has the potential to lead to better diagnosis, treatment planning, and monitoring for patients with TNBC.

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.

“Noninvasive imaging is essential for diagnosing and staging TNBC and predicting and measuring treatment response,” said Jason Lewis, Ph.D., Emily Tow Chair at Memorial Sloan Kettering Cancer Center in New York, New York.

“In our study, we sought to overcome tumor cell marker heterogeneity by developing an imaging agent that could detect multiple TNBC subtypes and improve diagnostic capacity.”

Researchers targeted extra domain A of fibronectin (EDA-FN), a stable protein in the tumor stromal environment which is abundantly expressed in breast cancer. A monoclonal antibody-based PET tracer ([⁸⁹Zr]Zr-DFO-F8) was created to detect EDA-FN. This tracer was then 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 Lewis.

“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.”

Provided by
Society of Nuclear Medicine and Molecular Imaging