Abstract 4239: Monitoring in vivo biodistribution of superparamagnetic nanoparticles using superparamagnetic relaxometry (SPMR) (2016)

Abstract We report on the use of Superparamagnetic Relaxometry (SPMR) as a technique for monitoring the distribution of superparamagnetic magnetite (Fe3O4) nanoparticles in vivo. SPMR uses superconducting quantum interference device (SQUID) sensors to measure the remnant magnetization of nanoparticles bound to cells following a brief magnetizing pulse. Unbound nanoparticles are not detected, making SPMR uniquely capable of discriminating between nanoparticles that are circulating freely in the bloodstream from those that have been immobilized in organs and tissues throughout the body. The rate of clearance of magnetic nanoparticles from circulation is largely dependent on their hydrodynamic diameter and surface chemistry. In this study, biodistribution of PrecisionMRX™ nanoparticles with 25 nm cores and two different surface coatings were followed using the MRX™ instrument. In independent experiments, negatively charged carboxylate nanoparticles and methoxy-PEG (mPEG) functionalized nanoparticles with a near neutral charge were suspended in 100 μL of saline. Nanoparticle suspensions were injected intravenously via tail vein into Balb/C mice at a dose of 5 mg/kg of body mass, while control mice were injected with 100 μL of saline solution. Mice were measured individually on the MRX instrument at successive time points over the course of 24 hours. At selected intervals during the 24 hour period, mice were euthanized, exsanguinated, and organs harvested for ex vivo measurements on the MRX. Organs and blood were subsequently assayed for iron content. MRX measurements of mice injected with carboxylate nanoparticles showed a strong magnetic signal localized in the region of liver that reached a maximum several minutes after injection. The negative surface charge of the carboxylate nanoparticles likely resulted in their rapid opsonization in the blood and removal from circulation by phagocytic cells in the liver. Conversely, MRX measurements of mice injected with mPEG coated nanoparticles indicated an extended circulation time, with a gradually increasing magnetic signal in the liver that had not yet reached a maximum after four hours. Together, these experiments demonstrate the utility in using SPMR to measure the clearance of nanoparticles from the bloodstream following injection, an important parameter in the design of optimal coatings for in vivo diagnostic and therapeutic use. This work was performed, in part, at the Center for Integrated Nanotechnologies, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. Citation Format: Andrew Gomez, Kayla E. Minser, Caroline L. Weldon, Bill Anderson, Todor Karaulanov, Helen J. Hathaway, Dale L. Huber, Edward R. Flynn, Erika Vreeland. Monitoring in vivo biodistribution of superparamagnetic nanoparticles using superparamagnetic relaxometry (SPMR). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4239.