Abstract P4-01-08: Specific detection of anti-Her2 PEGylated PrecisionMRX® nanoparticles measured using superparamagnetic relaxometry
Authors: CL Weldon, KE Minser, A Gomez, WH Anderson, T Karaulanov, HJ Hathaway, DL Huber, EC Vreeland, G Paciotti
Journal: Cancer Research (2017)

Abstract Current methods for detecting solid tumors lack sensitivity and diagnose primary and metastatic lesions only after the tumor is well established. Superparamagnetic Relaxometry (SPMR) is a combination technology that utilizes superconducting quantum interference detectors (SQUID) to measure the magnetization of superparamagnetic, tumor-targeting magnetite (Fe3O4) nanoparticles. Conceptually, PEGylated Fe3O4 nanoparticles labeled with a tumor targeting moiety (i.e., a monoclonal antibody) are intravenously injected and specifically target solid tumors utilizing both passive (the EPR effect) and active (receptor-mediated) mechanisms. Subsequently, the Fe3O4 nanoparticles are magnetized by a low field magnetic pulse in the MRX™ instrument and only those particles that are bound to their target site are measured by the SQUID sensors. Unbound nanoparticles are not detected. To demonstrate the utility of SPMR in detecting cancer we used PEGylated PrecisionMRX® nanoparticles that are covalently linked with a monoclonal antibody (mAb) targeting ERB-2 (anti-Her2). The particles were characterized for size (by dynamic light scattering), free and bound mAb (by ELISA), antibody potency (by bioassay) and stealth (in plasma interaction studies). In vitro, the anti-Her2 conjugated particles exhibited specific binding to ERB-2 overexpressing breast cancer cells (MCF-7/Her2-18). Specific binding was defined by the ability of the native mAb to competitively block the binding of the anti-HER-2 conjugated particles to ERB-2 antigen coated on ELISA plates or expressed on the cell surface. In addition, in ERB-2 negative cell lines, the anti-Her2 conjugated particles exhibited little to no binding. In vivo, anti-Her2 conjugated PrecisionMRX exhibited significantly longer circulation times when compared to unPEGylated particles. Distinct magnetic dipoles were detected by the MRX instrument at the target site (the tumor) and site of nanoparticle elimination (the liver). These data were confirmed in excised organs showing significant magnetic moments in the liver, tumor, and spleen. Analysis of the MRX SPMR data suggest that the technology can detect as few as 10,000 cancer cells in vivo by optimizing the nanoparticles for stealth and targeting. 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: Weldon CL, Minser KE, Gomez A, Anderson WH, Karaulanov T, Hathaway HJ, Huber DL, Vreeland EC, Paciotti G. Specific detection of anti-Her2 PEGylated PrecisionMRX® nanoparticles measured using superparamagnetic relaxometry [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-01-08.