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

Reston, VA (June 4, 2025)—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. 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, PhD, 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.”

Visual Abstract.  [⁸⁹Zr]Zr-DFO-F8 binds specifically with EDA-FN in the tumor stroma to delineate TNBC.

The authors of “Targeting Extra Domain A of Fibronectin to Improve Noninvasive Detection of Triple-Negative Breast Cancer” include Justin S. Hachey, Department of Pharmacology, Weill Cornell Graduate School of Medical Sciences, New York, New York, and Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; Tara D. Viray, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; Mattia Matasci and Domenico Ravazza, Philochem AG, Otelfingen, Switzerland; Dario Neri, Philogen S.p.A, Siena, Italy, and Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Zurich, Switzerland; and Jason S. Lewis, Department of Pharmacology, Weill Cornell Graduate School of Medical Sciences, New York, New York, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, and Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.

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Please visit the SNMMI Media Centerfor more information about molecular imaging and precision imaging. To schedule an interview with the researchers, please contact Rebecca Maxey at (703) 652-6772 or [email protected].

About JNM and the Society of Nuclear Medicine and Molecular Imaging

The Journal of Nuclear Medicine (JNM) is the world’s leading nuclear medicine, molecular imaging and theranostics journal, accessed 15 million times each year by practitioners around the globe, providing them with the information they need to advance this rapidly expanding field. Current and past issues of The Journal of Nuclear Medicine can be found online at http://jnm.snmjournals.org.

JNM is published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an international scientific and medical organization dedicated to advancing nuclear medicine, molecular imaging, and theranostics—precision medicine that allows diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes. For more information, visit www.snmmi.org.