Targeting extra domain a of fibronectin to improve noninvasive detection of triple-negative breast cancer Journal Article

   


Authors: Hachey, J. S.; Viray, T. D.; Matasci, M.; Ravazza, D.; Neri, D.; Lewis, J. S.
Article Title: Targeting extra domain a of fibronectin to improve noninvasive detection of triple-negative breast cancer
Abstract: Triple-negative breast cancer (TNBC) lags behind other breast cancer types in targeted therapeutic and diagnostic imaging agent development, largely due to high disease heterogeneity. Noninvasive imaging is essential for diagnosing and staging TNBC and predicting and measuring treatment response. This study targeted a conserved disease-specific extracellular matrix protein domain (the extra domain A of fibronectin [EDA-FN]), with a monoclonal antibody (F8) to overcome tumor cell marker heterogeneity and develop an imaging agent to detect multiple TNBC subtypes and improve diagnostic capacity. Methods: [89Zr]Zr-desferrioxamine [DFO]-F8 was synthesized and evaluated in vitro and in vivo for EDA-FN binding capacity to detect TNBC by PET/CT in several preclinical xenograft models. Results: [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 detected EDA-FN in subcutaneous and orthotopic TNBC xenografts and accumulated in aggressive disease concordantly with EDA-FN expression. Conclusion: EDA-FN imaging with [89Zr]Zr-DFO-F8 exhibits powerful tumor delineation in preclinical tumor delineation across TNBC molecular subtypes in vivo. COPYRIGHT © 2025 by the Society of Nuclear Medicine and Molecular Imaging.
Keywords: controlled study; protein expression; human cell; nonhuman; protein domain; animal cell; mouse; animal; metabolism; animals; mice; animal tissue; cell viability; tumor volume; interleukin 13; interleukin 1beta; interleukin 8; animal experiment; animal model; in vivo study; immunofluorescence; in vitro study; tumor xenograft; cell line, tumor; diagnostic imaging; monoclonal antibody; extracellular matrix; toll like receptor 4; antibodies, monoclonal; chemistry; tumor cell line; interleukin 6; radioisotope; tumor growth; pet; radioisotopes; thin layer chromatography; toll like receptor 2; zirconium; zirconium-89; deferoxamine; fibronectin; protein domains; cancer growth factor; triple negative breast cancer; affinity chromatography; toll like receptor 5; procedures; fibronectins; humans; human; female; article; positron emission tomography-computed tomography; positron emission tomography computed tomography; triple negative breast neoplasms; tnbc; tumor necrosis factor alpha receptor
Journal Title: Journal of Nuclear Medicine
Volume: 66
Issue: 6
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2025-06-01
Start Page: 880
End Page: 885
Language: English
DOI: 10.2967/jnumed.124.268859
PUBMED: 40246542
PROVIDER: scopus
PMCID: PMC12176004
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-105007319949&doi=10.2967%2fjnumed.124.268859&partnerID=40&md5=1e2c696eebabcb360ef4640e0ae7c62e
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Jason S. Lewis -- Source: Scopus
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MSK Authors
  1. Jason S Lewis
    460 Lewis
  2. Tara Viray
    13 Viray
  3. Justin Hachey
    2 Hachey
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