Nanotheranostics 2021; 5(2):240-255. doi:10.7150/ntno.50721

Research Paper

Non-radioactive and sensitive tracking of neutrophils towards inflammation using antibody functionalized magnetic particle imaging tracers

Prashant Chandrasekharan1*✉, K.L. Barry Fung1,2 *✉, Xinyi Y. Zhou1,2*, Weiwen Cui1, Caylin Colson1,2, David Mai1, Kenneth Jeffris1, Quincy Huynh3, Chinmoy Saayujya3, Leyla Kabuli1, Benjamin Fellows1, Yao Lu1, Elaine Yu1, Zhi Wei Tay1, Bo Zheng1, Lawrence Fong4, Steven M. Conolly1,3

1. Department of Bioengineering, University of California, Berkeley, California 94720, United States.
2. UC Berkeley-UCSF Graduate Group in Bioengineering, California, United States.
3. Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, United States.
4. UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143, United States.
*These authors contributed equally to this work.

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Citation:
Chandrasekharan P, Fung KLB, Zhou XY, Cui W, Colson C, Mai D, Jeffris K, Huynh Q, Saayujya C, Kabuli L, Fellows B, Lu Y, Yu E, Tay ZW, Zheng B, Fong L, Conolly SM. Non-radioactive and sensitive tracking of neutrophils towards inflammation using antibody functionalized magnetic particle imaging tracers. Nanotheranostics 2021; 5(2):240-255. doi:10.7150/ntno.50721. Available from https://www.ntno.org/v05p0240.htm

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Abstract

White blood cells (WBCs) are a key component of the mammalian immune system and play an essential role in surveillance, defense, and adaptation against foreign pathogens. Apart from their roles in the active combat of infection and the development of adaptive immunity, immune cells are also involved in tumor development and metastasis. Antibody-based therapeutics have been developed to regulate (i.e. selectively activate or inhibit immune function) and harness immune cells to fight malignancy. Alternatively, non-invasive tracking of WBC distribution can diagnose inflammation, infection, fevers of unknown origin (FUOs), and cancer. Magnetic Particle Imaging (MPI) is a non-invasive, non-radioactive, and sensitive medical imaging technique that uses safe superparamagnetic iron oxide nanoparticles (SPIOs) as tracers. MPI has previously been shown to track therapeutic stem cells for over 87 days with a ~200 cell detection limit. In the current work, we utilized antibody-conjugated SPIOs specific to neutrophils for in situ labeling, and non-invasive and radiation-free tracking of these inflammatory cells to sites of infection and inflammation in an in vivo murine model of lipopolysaccharide-induced myositis. MPI showed sensitive detection of inflammation with a contrast-to-noise ratio of ~8-13.

Keywords: magnetic particle imaging, white blood cells, antibody, medical imaging, inflammation, superparamagnetic iron oxide nanoparticles