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

Z Zhou, M Qutaish, Z Han, RM Schur, Y Liu… - Nature …, 2015 - nature.com
Z Zhou, M Qutaish, Z Han, RM Schur, Y Liu, DL Wilson, ZR Lu
Nature communications, 2015nature.com
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 …
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.
nature.com