An Optimized Integrin α6-Targeted Magnetic Resonance Probe for Molecular Imaging of Hepatocellular Carcinoma in Mice

摘要

Introduction: Integrin alpha 6 is an attractive diagnostic biomarker for molecular imaging of hepatocellular carcinoma (HCC) as it has an extremely high positive rate (approximately 94%) in clinical early-stage HCC. In this study, based on our previously identified integrin a6-targeted peptide, we developed an optimized integrin alpha 6-targeted magnetic resonance (MR) probe dubbed DOTA(Gd)-ANADYWR for MR imaging of HCC in mice. Materials and Methods: The longitudinal (R-1) relaxivity of DOTA(Gd)-ANADYWR was measured on a 3.0 T MR system. The specific tumor enhancement of the agent was investigated in four distinct mouse models, including subcutaneous, orthotopic, genetically engineered and chemically induced HCC mice. Results: The R-1 relaxivity value of DOTA(Gd)-ANADYWR is 5.11 mM(-1)s(-1) at 3.0 T, which is similar to that of the nonspecific clinical agent Gadoteridol. DOTA(Gd)-ANADYWR generated superior enhanced MR signal in HCC lesions and provided complementary enhancement MR signals to the clinically available hepatobiliary MR contrast agent gadoxetate disodium (GdEOB-DTPA). Importantly, DOTA(Gd)-ANADYWR could efficiently visualize small HCC lesion (approximately 1 mm) which was hardly detected by the clinical Gd-EOB-DTPA. Conclusion: These findings suggest the potential application of this integrin alpha 6-targeted MR probe for the detection of HCC, particularly for small HCC.

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