Integrin α6-Targeted Magnetic Resonance Imaging of Hepatocellular Carcinoma in Mice

Purpose Magnetic resonance imaging (MRI) has a high spatial resolution for detecting hepatocellular carcinoma (HCC). Integrin alpha 6 has emerged as a diagnostic and prognostic biomarker of HCC. Here, we developed the MR contrast agent RWY-dL-(Gd-DOTA)(4) based on the integrin alpha 6-targeted RWY peptide that we previously identified to detect HCC. Procedures Contrast-enhanced MRI was carried out to evaluate the use of RWY-dL-(Gd-DOTA)(4) to detect HCC lesions in subcutaneous and diethylnitrosamine (DEN)-induced HCC mouse models. Results Enhancement MR signals were observed in HCC-LM3 subcutaneous liver tumors in the first 5 min post-injection of RWY-dL-(Gd-DOTA)(4) at a low dose of 0.03 mmol Gd/kg. Moreover, RWY-dL-(Gd-DOTA)(4) generated superior contrast enhancement for liver tumors in chemical-induced HCC mice. Importantly, RWY-dL-(Gd-DOTA)(4) provided complementary enhancement MR signals to the clinical available hepatobiliary MR contrast agent gadoxetate disodium Gd-EOB-DTPA. Additionally, RWY-dL-(Gd-DOTA)(4) showed minimal gadolinium retention in normal tissues and organs at 48 h post-injection. Conclusion These findings potentiate the use of RWY-dL-(Gd-DOTA)(4) for the MRI of HCC to improve the diagnosis of HCC.