Cell Labeling via Membrane-Anchored Lipophilic MR Contrast Agents

Abstract

Cell tracking <i>in vivo</i> with MR imaging requires the development of contrast agents with increased sensitivity that effectively label and are <i>retained</i> by cells. Most clinically approved Gd­(III)-based contrast agents require high incubation concentrations and prolonged incubation times for cellular internalization. Strategies to increase contrast agent permeability have included conjugating Gd­(III) complexes to cell penetrating peptides, nanoparticles, and small molecules which have greatly improved cell labeling but have not resulted in improved cellular retention. To overcome these challenges, we have synthesized a series of lipophilic Gd­(III)-based MR contrast agents that label cell membranes <i>in vitro</i>. Two of the agents were synthesized with a multiplexing strategy to contain three Gd­(III) chelates (<b>1</b> and <b>2</b>) while the third contains a single Gd­(III) chelate (<b>3</b>). These new agents exhibit significantly enhanced labeling and retention in HeLa and MDA-MB-231-mcherry cells compared to agents that are internalized by cells (<b>4</b> and Prohance)