nCP:Fe Nanocontrast Agent for Magnetic Resonance Imaging-Based Early Detection of Liver Cirrhosis and Hepatocellular Carcinoma.

Early detection of liver tumors and cirrhotic lesions by magnetic resonance imaging (MRI) remains a great challenge. Here, we report a biomineral nanocontrast agent based on iron-doped nanocalcium phosphate (nCP:Fe-CA) for magnetic resonance imaging of early-stage liver cirrhotic and hepatocellular carcinoma nodules using rat models. We have optimized an intravenously injectable, aqueous suspension of nCP:Fe-CA having an average size of 137.6 nm, a spherical shape, magnetic relaxivity of 63 mMS, and colloidal stability for 48 h, post-resuspension in an aqueous phase. Compared to superparamagnetic iron oxide nanoparticles (SPIONs), the optimized nCP:Fe-CA could detect liver tumor lesions as small as ∼0.25 cm, whereas the current clinical detection limit is ∼1 cm. In addition, multiple cirrhotic nodules of size <0.2 cm could be detected by nCP:Fe-CA-assisted MRI. The number of nodules observed after injecting nCP:Fe-CA was ∼3 times higher than that without CA (5-10 nodules). A biocompatibility study on healthy rats injected with nCP:Fe-CA showed unaltered liver transaminases, blood urea nitrogen, serum creatinine, and insignificant hemolysis. Furthermore, hepatobiliary clearance of nCP:Fe-CA was observed in 72 h compared to prolonged retention of SPIONs for 30 days when tested under identical conditions. Overall, the nCP:Fe-CA nanoparticles showed promising results as a biocompatible, MR contrast (T2) agent for the early-stage imaging of liver cirrhosis and hepatocellular carcinoma.