Abstract 2770: Imaging cancer immunology: Monitoring CD47 mAb treatment in vivo by magnetic particle imaging
Authors: Ren Gang , Gaudet Jeff M. , Gerosa Marco , Zhang Yanrong , Mansfield James , Wintermark Max , Goodwill Patrick 
Published: September 2020

Abstract
Introduction: The rapid growth of research into immuno-oncology research has fueled a need to be able to evaluate the efficacy of immunotherapies in a timely and comprehensive fashion. However, established non-invasive imaging approaches have been insufficient to meet all requirements. Magnetic Particle Imaging (MPI) is a novel tomographic molecular imaging technique that can be used to track iron-oxide in 3D in vivo, with sensitivity and specificity similar to nuclear medicine but without the complex workflow, safety, and half-life limitations.
Methods: A murine breast tumor model was established by injecting 3 × 105 4T1 cells into the 4th mammary fat pad of 8-10 week female Blab/c mice. A CD47 monoclonal antibody (mAb) treatment was initiated by intraperitoneal injection of CD47 mAb (Bio-X Cell) at day 6 after tumor implantation. The treated and the control groups were then injected with an iron-oxide MPI tracer (6mg/kg) and then 3D MPI images were acquired 8, 11, 14 and 17 days after implantation. µCT and MRI were also acquired with a T2-weighted multi-slice, multi-echo (MSME) sequences at above time points. Both MPI and MRI images were co-registered and quantified. Tumors, liver, spleen and draining lymph nodes were then harvested, imaged, fixed, and stained with Perls Prussian blue.
Results: Superparamagnetic iron oxide nanoparticles accumulation has been shown qualitatively to increase following CD47 mAb treatment [1]. To determine iron accumulation within the tumor, MPI was co-registered to both MRI µCT for anatomical context. All mice showed an accumulation of nanoparticles in the tumor and liver following injection in both MRI and MPI. Quantitation of iron at the tumor was performed and compared between the CD47-treated and untreated groups at every imaging time point with MPI. CD47 mAb treated breast tumors demonstrated enhanced positive contrast on 3D MPI images while a shortened T2 relaxation on MRI images. Iron content within the tumor was confirmed by ex vivo scanning followed by staining.
Conclusions: By combining the sensitivity, specificity and quantitation potentials of MPI, information can be obtained on a preclinical model that monitors the efficacy of CD47 mAb cancer immunotherapy. With the high spatial resolution provided by MRI, coregistered MRI-MPI can be utilized to evaluate the response of tumor-associated macrophages to CD47 mAb and other cancer immunotherapies.
References: 1. Mohanty S, et al. Nanoparticle enhanced MRI can monitor macrophage response to CD47 mAb immunotherapy in osteosarcoma. Cell Death Dis. 2019;10(2):36. Published 2019 Jan 15. doi:10.1038/s41419-018-1285-3
Citation Format: Gang Ren, Jeff M. Gaudet, Marco Gerosa, Yanrong Zhang, James Mansfield, Max Wintermark, Patrick Goodwill. Imaging cancer immunology: Monitoring CD47 mAb treatment in vivo by magnetic particle imaging [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2770.