Decreased Reticuloendothelial System Clearance and Increased Blood Half-Life and Immune Cell Labeling for Nano- And Micron-Sized MRI Contrast Agents Upon Pre-Treatment with Intralipid

Li Liu¹, T Kevin Hitchens¹, Qing Ye¹, Yijen Wu¹, Brent D. Barbe¹, Devin E. Prior¹, Wendy Fei Li¹, Lesley M. Foley¹, Frank Fang-Cheng Yeh¹, Daniel J. Bain², Chien Ho¹

Non-invasive in-vivo MRI of monocytes/macrophages labeled with MRI contrast agents may lead to a better understanding of the pathogenesis of many diseases. MRI contrast agents are taken up by the reticuloendothelial system, in particular by liver Kupffer cells, which often contribute to the major loss of the agents in circulation. Strategies that reduce liver uptake and prolong the circulation residence time of these MRI contrast agents can improve the in-vivo labeling efficiency of monocytes/macrophages and lower the required effective dose. In this study, we found that pre-treatment with Intralipid, FDA approved fat emulsion, can result a ~50% decrease in liver uptake of nano- and micron-sized superparamagnetic iron-oxide based MRI contrast agents, resulting a ~3-fold increase in blood half-life and a 2- to 5-fold increase in the labeling efficiency of monocytes in the peripheral blood.