MRI contrast enhancement of liver pre-neoplasia using iron-tannic nanoparticles

The most challenging part of liver cancer detection is finding it in the very early stages. It has been argued that liver preneoplasia is found at the very earliest stages of liver cancer. The presence of a lesion is closely related to the development of HCC. We report herein a new class of iron-based T₁ MRI contrast agents which are nanoparticles of iron-tannic complexes (so-called Fe-TA NPs) that can be used for detecting liver preneoplasia. Preliminary assessment of their toxicity in healthy rats provides suitable imaging dose ranges with acceptable toxicity. In diethylnitrosamine (DEN) induced rats, it is shown that Fe-TA NPs are capable of enhancing MRI signals in rat livers having pre-neoplastic lesions within 60 minutes post-injection. The enhancement efficacy is strongly dependent on the characteristics of pre-neoplastic foci (GST-P+ foci). The highest enhancement was in good correlation with the size of GST-P+ foci and amount of Fe-TA NPs accumulated in the liver, and might be caused by the dysfunction of liver sinusoids along with cellular uptake capability of pre-neoplastic hepatocytes. Our results show that Fe-TA NPs are of great interest to develop as an efficient MRI imaging agent for risk assessment of liver cancer.