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Alexandra Jones

Health Sciences, '19


Investigating the use of Feraheme to monitor the immune response by PET in general inflammation and specific immune cell populations

Mentor: Georges El Fakhri, Ph.D. (MGH)

Feraheme (FH), an FDA approved nanoparticle drug to treat iron anemia, has an off label application as an MRI contrast agent for the blood pool. This nanoparticle is also selectively phagocytized by monocytes and macrophages, allowing it to be used as an MRI contrast agent for those cell populations. Previous research has shown that FH can be labeled with radionuclides to track monocytes and macrophages using Positron Emission Tomography (PET) [1]. In addition to its ability to track monocytes and macrophages, FH can be modified with functional groups, which allows the drug to target additional immune cell populations such as B and T cells, and neutrophils [2]. Almost every disease has an immune component, whether it’s an overreaction seen in vulnerable plaques of atherosclerosis, or in autoimmune responses, or an insufficient immune response as seen in cancer. Therefore, the development of the non-invasive methods to track and monitor the immune response would be of significant interest in the clinical setting. We will use FH and microPET imaging to monitor the response of monocytes and macrophages in a mouse model of general inflammation. Monitoring will be performed across various strains of immuno-competent and immuno-compromised mice. The development of monocyte/macrophage imaging will have particular significance in the area of cardiovascular imaging, specifically in monitoring the inflammatory response from vulnerable plaques. These plaques heavily integrate CD68+ macrophages, which could be monitored with PET imaging using radioactive FH, to determine where and to what extent, these plaques are present in a patient. In addition to studying general inflammation, the ability to target and monitor other specific immune cell populations, such as B and T cells, could have significant clinical applications. We will investigate these applications using a mouse model of Multiple Sclerosis (MS). Using published methods to track lymphocytes via PET [3], we will image the B-cell response in the experimental autoimmune encephalomyelitis (EAE) model of MS, to track the course of B-cell infiltration over the course of this auto-immune disease. [1] Marc D. Normandin, Hushan Yuan, Moses Q. Wilks, Howard H. Chen, Joseph M. Kinsella, Hoonsung Cho, Nicolas J. Guehl, Nader Absi-Halabi, Seyed Mohammadreza Hosseini, Georges El Fakhri, DavidE. Sosnovik, and Lee Josephson. Angew. Chem. 2015, 127, 13194–13198. [2] Yuan H, Wilks MQ, El Fakhri G, Normandin MD, Kaittanis C, Josephson L (2017) Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials. PLoS ONE 12(2): e0172722. doi:10.1371/journal.pone.0172722 [3] Ruxandra F. Sirbulescu, PhD; Chloe K. Boehm; Erin Soon, BSc; Moses Q. Wilks, PhD; Iulian Ilies ̧ PhD; Hushan Yuan, PhD; Ben Maxner, BS; Nicolas Chronos, MD; Charalambos Kaittanis, PhD; Marc D. Normandin, PhD; Georges El Fakhri, PhD; Dennis P. Orgill, MD, PhD; Ann E. Sluder, PhD; Mark C. Poznansky, MB, ChB, PhD Wound Rep Reg (2017) 25 774–791.