MRI detection of breast cancer micrometastases with a fibronectin-targeting contrast agent

Zhuxian Zhou, Mohammed Qutaish, Zheng Han, Rebecca M. Schur, Yiqiao Liu, David L. Wilson () and Zheng-Rong Lu ()
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Zhuxian Zhou: Case Western Reserve University
Mohammed Qutaish: Case Western Reserve University
Zheng Han: Case Western Reserve University
Rebecca M. Schur: Case Western Reserve University
Yiqiao Liu: Case Western Reserve University
David L. Wilson: Case Western Reserve University
Zheng-Rong Lu: Case Western Reserve University

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract Metastasis is the primary cause of death in breast cancer patients. Early detection of high-risk breast cancer, including micrometastasis, is critical in tailoring appropriate and effective interventional therapies. Increased fibronectin expression, a hallmark of epithelial-to-mesenchymal transition, is associated with high-risk breast cancer and metastasis. We have previously developed a penta-peptide CREKA (Cys-Arg-Glu-Lys-Ala)-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agent, CREKA-Tris(Gd-DOTA)3 (Gd-DOTA (4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecyl gadolinium), which binds to fibrin–fibronectin complexes that are abundant in the tumour microenvironment of fast-growing breast cancer. Here we assess the capability of CREKA-Tris(Gd-DOTA)3 to detect micrometastasis with MRI in co-registration with high-resolution fluorescence cryo-imaging in female mice bearing metastatic 4T1 breast tumours. We find that CREKA-Tris(Gd-DOTA)3 provides robust contrast enhancement in the metastatic tumours and enables the detection of micrometastases of size

Date: 2015
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DOI: 10.1038/ncomms8984

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