Abstract 1865: Enhancing the in vivo detection of cancer by manipulating magnetic fields applied to tumor targeting superparamagnetic iron oxide nanoparticles

Abstract

Abstract Superparamagnetic Relaxometry (SPMR) is combination technology for the early detection of cancer. Conceptually, PEGylated superparamagnetic iron oxide (Fe3O4) nanoparticles (NPs) coupled with a tumor targeting monoclonal antibody are systemically administered and target solid tumors by both passive (EPR) and active (receptor targeting) mechanisms. Once bound to the target cells, the NPs are magnetized by a brief, low field magnetic pulse to create macroscopic magnetization. Once the field is removed, the particle’s magnetization decays and is measurable by superconducting quantum interference device (SQUID) detectors. The pattern of decay, known as Néel relaxation, exhibits a difference in latency specific to bound nanoparticles and differs from the Brownian decay exhibited by free/unbound particles. As a proof of concept, we developed PEGylated NPs that are covalently bound to an anti-Her-2 monoclonal antibody. In vitro, the nanoconstruct exhibits specific binding to the Her-2 overexpressing BT-474 breast cancer cells, with little to no binding to Her-2 negative MCF-7cells. Similar patterns of selective targeting were observed in vivo. To improve the specific detection of SPMR signals in tumors we developed a novel system that selectively enhances the magnetic signal at tumor sites and reduces the contribution of similar signals at off target sites such as the liver and spleen. For these studies, we created phantoms of varying strength to mimic tumor and non-specific signals. We observed that by creating non-homogenous excitation magnetic field patterns, we reduced the contribution of the non-specific signals by an order of magnitude, effectively increasing the signal to noise ratio of the tumor signal. These results are clinically relevant and support the use of SPMR in the detection of small tumors in cancer patients. Citation Format: Todor Karaulanov, Erika C. Vreeland, Andrew Gomez, Kayla E. Minser, Caroline L. Weldon, William H. Anderson, Christopher Nettles, Giulio Paciotti. Enhancing the in vivo detection of cancer by manipulating magnetic fields applied to tumor targeting superparamagnetic iron oxide nanoparticles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1865. doi:10.1158/1538-7445.AM2017-1865