Abstract P6-01-05: Detection of HER2 positive tumor cells using functionalized iron oxide nanoparticles

Abstract

Abstract Background: Iron oxide nanoparticles (NPs) have been used for a variety of in-vivo and ex-vivo applications within the biomedical sciences. Moreover, when intended for clinical in-vivo applications, NPs need to meet rigorous requirements to ensure safety as well as bio-functionality including blood circulation time and specificity for cellular targets. PrecisonMRX® NPs are extensively characterized superparamagnetic NPs composed of a 25nm magnetite cores that are currently employed in a variety of in-vivo applications including non-invasive/in vivo diagnosis of cancer, Magnetic Particle Imaging, MRI, and magnetic hyperthermia. Objective: Here we report on the extensive pre-clinical development and functionality of antibody (Herceptin)-conjugated NPs for in-vivo and ex-vivo detection of HER2+ tumor cells by Magnetic Relaxometry (MRX). Results: We observed: 1) specific binding and detection of HER2 positive tumor cells in-vitro; 2) specific detection of HER2+ tumors in mice; 3) binding and amplitude of magnetic signal to be proportional to the level of HER2 expression in-vitro and in-vivo; 4) the nanoconstruct remains stable in circulation; 5) the particles do not induce a pro-inflammatory response nor activate complement; 6) the particles are biodegradable; and do not induce acute or delayed signs of morbidity in mice. Conclusion: Precision MRX® nanoparticles offer great clinical promise including the in- vivo detection of tumor cells by magnetic relaxometry. Given the stability and safety of these NPs, our pre-clinical results support progressing to clinical testing. A first-in human ex-vivo clinical research study design and strategy will be discussed. Citation Format: Bischoff FZ, Mathieu K, Vargas J, Pang L, Kulp AM, Dewing A, Liu X, Bast RC, Hazle J, Zhang M. Detection of HER2 positive tumor cells using functionalized iron oxide nanoparticles [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-01-05.