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 α6 has emerged as a diagnostic and prognostic biomarker of HCC. Here, we developed the MR contrast agent RWY-dL-(Gd-DOTA) based on the integrin α6-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) 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) at a low dose of 0.03 mmol Gd/kg. Moreover, RWY-dL-(Gd-DOTA) generated superior contrast enhancement for liver tumors in chemical-induced HCC mice. Importantly, RWY-dL-(Gd-DOTA) provided complementary enhancement MR signals to the clinical available hepatobiliary MR contrast agent gadoxetate disodium Gd-EOB-DTPA. Additionally, RWY-dL-(Gd-DOTA) 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) for the MRI of HCC to improve the diagnosis of HCC.