MR Molecular Imaging of Breast Cancer Metastases with Peptide Targeted Tripod Macrocyclic Gd(III) Chelates

MRI is a powerful medical imaging modality for the detection and characterization of diseased soft tissues such as solid tumors. MR molecular imaging has a great potential for detection and characterization of metastatic breast cancer if a suitable molecular target can be identified. However, currently available targeted contrast agents could not generate sufficient contrast enhancement for molecular MRI of the biomarkers on cancer cell surface due to low concentration of the biomarkers and low sensitivity of MRI. The extracellular matrix of malignant tumors has abundant accumulation of fibrin-fibronectin complexes that can be used as a suitable biomarker for effective molecular MRI of small breast cancer metastases. CREKA is a tumor-homing pentapeptide (Cys-Arg-Glu-Lys-Ala) specifically homes to tumors by binding to fibrin and fibronectin associated plasma protein clots in tumor stroma. Here, we synthesized and evaluated a tumor-targeted contrast agent CREKA-Tris(Gd-DOTA)3 for MR molecular imaging of breast cancer metastases.

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