Active-target T₁-weighted MR Imaging of Tiny Hepatic Tumor via RGD Modified Ultra-small Fe₃O₄ Nanoprobes

摘要

Developing ultrasensitive contrast agents for the early detection of malignant tumors in liver is highly demanded. Constructing hepatic tumors specific targeting probes could provide more sensitive imaging information but still faces great challenges. Here we report a novel approach for the synthesis of ultra-small Fe₃O₄ nanoparticles conjugated with c(RGDyK) and their applications as active-target T₁-weighted magnetic resonance imaging (MRI) contrast agent (T₁-Fe₃O₄) for imaging tiny hepatic tumors in vivo . RGD-modified T₁-Fe₃O₄ nanoprobes exhibited high r₁ of 7.74 mM-1s-1 and ultralow r₂/r₁ of 2.8 at 3 T, reflecting their excellent T₁ contrast effect at clinically relevant magnetic field. High targeting specificity together with favorable biocompatibility and strong ability to resist against non-specific uptake were evaluated through in vitro studies. Owing to the outstanding properties of tumor angiogenesis targeting with little phagocytosis in liver parenchyma, hepatic tumor as small as 2.2 mm was successfully detected via the T₁ contrast enhancement of RGD-modified T₁-Fe₃O₄. It is emphasized that this is the first report on active-target T₁ imaging of hepatic tumors, which could not only significantly improve diagnostic sensitivity, but also provide post therapeutic assessments for patients with liver cancer.