Magnetic Resonance Imaging of Macrophage Response to Radiation Therapy

Author:

Yang Harrison1,Howerton Brock2,Brown Logan1,Izumi Tadahide34ORCID,Cheek Dennis5,Brandon J. Anthony6,Marti Francesc37,Gedaly Roberto37,Adatorwovor Reuben8ORCID,Chapelin Fanny29

Affiliation:

1. F. Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40506, USA

2. Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA

3. Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA

4. Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA

5. Department of Radiation Medicine, University of Kentucky, Lexington, KY 40536, USA

6. Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40508, USA

7. Department of Surgery, Transplant Division, University of Kentucky, Lexington, KY 40506, USA

8. Department of Biostatistics, University of Kentucky, Lexington, KY 40536, USA

9. Department of Radiology, University of California San Diego, La Jolla, CA 92093, USA

Abstract

Background: Magnetic resonance imaging (MRI) is a non-invasive imaging modality which, in conjunction with biopsies, provide a qualitative assessment of tumor response to treatment. Intravenous injection of contrast agents such as fluorine (19F) nanoemulsions labels systemic macrophages, which can, then, be tracked in real time with MRI. This method can provide quantifiable insights into the behavior of tumor-associated macrophages (TAMs) in the tumor microenvironment and macrophage recruitment during therapy. Methods: Female mice received mammary fat pad injections of murine breast or colon cancer cell lines. The mice then received an intravenous 19F nanoemulsion injection, followed by a baseline 19F MRI. For each cancer model, half of the mice then received 8 Gy of localized radiation therapy (RT), while others remained untreated. The mice were monitored for two weeks for tumor growth and 9F signal using MRI. Results: Across both cohorts, the RT-treated groups presented significant tumor growth reduction or arrest, contrary to the untreated groups. Similarly, the fluorine signal in treated groups increased significantly as early as four days post therapy. The fluorine signal change correlated to tumor volumes irrespective of time. Conclusion: These results demonstrate the potential of 19F MRI to non-invasively track macrophages during radiation therapy and its prognostic value with regard to tumor growth.

Funder

National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health

American Cancer Society

Shared Resource Facilities of the University of Kentucky Markey Cancer Center

Commonwealth Undergraduate Research Experience (CURE) Fellowship

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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