Synthesis of Ultrasmall Fe₃O₄ Nanoparticles as <i>T</i>₁–<i>T</i>₂ Dual-Modal Magnetic Resonance Imaging Contrast Agents in Rabbit Hepatic Tumors

Abstract

To elevate the accurate diagnosis of tumors, nanomaterial-based magnetic resonance imaging (MRI) contrast agents are being rapidly developed. In this paper, we report the large-scale synthetic method of Fe3O4 nanoparticles by high-temperature thermal decomposition and their application as time-dependent T1–T2 dual-modal MRI contrast agents in rabbit hepatic tumors. The Fe3O4 nanoparticles are modified with bull serum albumin (BSA), which provides excellent biocompatibility and colloidal stability. These nanoparticles also exhibit a high r1 value of 6.99 mM–1 s–1 and a low r2 value of 24.11 mM–1 s–1 at a clinically relevant magnetic field (3.0 T). In in vivo experiments, after intravenous administration with these nanoparticles, the rapid T2-weighted effect can be acquired within 5 min and the slow T1 contrast enhancement at the tumor site appears at 90 min. The explanation of this phenomenon is possibly due to the different accumulation rates and states of the nanoparticles in different tissues. In normal liver tissue, the nanoparticles can be quickly phagocytosed by a reticuloendothelial system and accumulated in the liver. These accumulated nanoparticles aggregate, improving the T2-weighted effect and reducing the T1-weighted effect. However, because of an enhanced permeation and retention effect, the nanoparticles are delivered into tumor tissue gradually and dispersedly, which takes a longer time to generate the T1-weighted effect at the tumor site. In summary, these Fe3O4 nanoparticles have significant potential to improve the diagnostic accuracy and sensitivity in MRI.