Furin-Catalyzed Enhanced Magnetic Resonance Imaging Probe for Differential Diagnosis of Malignant Breast Cancers.

Abstract

Molecular magnetic resonance imaging (mMRI) of biomarkers is essential for accurate cancer detection in precision medicine. However, the current clinically used contrast agents provide structural magnetic resonance imaging (sMRI) information only and rarely provide mMRI information. Here, a tumor-specific furin-catalyzed nanoprobe (NP) was reported for differential diagnosis of malignant breast cancers (BCs) in vivo. This NP with a compact structure of Fe3O4@Gd-DOTA NPs (FFG NPs) contains an "always-on" T2-weighted MR signal provided by the magnetic Fe3O4 core and a furin-catalyzed enhanced T1-weighted MR signal provided by the Gd-DOTA moiety. The FFG NPs were found to produce an activated T1 signal in the presence of furin catalysis and an "always-on" T2 signal, providing mMRI and sMRI information simultaneously. Ratiometric mMRI:sMRI intensity can be used for differential diagnosis of malignant BCs MDA-MB-231 and MCF-7, where the furin levels relatively differ. The proposed probe not only provides structural imaging but also enables real-time molecular differential visualization of BC through enzymatic activities of cancer tissues.