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

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 <0.5 mm, extending the detection limit of the current clinical imaging modalities. These results demonstrate that molecular MRI with CREKA-Tris(Gd-DOTA)3 may facilitate early detection of high-risk breast cancer and micrometastasis in the clinic.

• Authors: Zhuxian Zhou, Mohammed Qutaish, Zheng Han, Rebecca M Schur, Yiqiao Liu, David L Wilson, Zheng-Rong Lu
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 7984 (Aug 12 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 26264658 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• CREKA-Tris(Gd-DOTA)3
• Contrast Media
• Coordination Complexes
• Fibronectins
• Oligopeptides

Topics

• Animals
• Cell Line, Tumor
• Contrast Media (chemistry, pharmacology)
• Coordination Complexes (chemistry, pharmacology)
• Female
• Fibronectins (chemistry, metabolism)
• Humans
• Magnetic Resonance Imaging (methods)
• Mammary Neoplasms, Animal (pathology)
• Mice
• Mice, Nude
• Neoplasms, Experimental (pathology)
• Oligopeptides (chemistry, pharmacology)
• Tissue Distribution