Theranostics 2017; 7(4):926-934. doi:10.7150/thno.17131

Research Paper

Visualization of Macrophage Recruitment to Inflammation Lesions using Highly Sensitive and Stable Radionuclide-Embedded Gold Nanoparticles as a Nuclear Bio-Imaging Platform

Sang Bong Lee1,2*, Ho Won Lee1*, Thoudam Debraj Singh1, Yinghua Li3, Sang Kyoon Kim9, Sung Jin Cho4, Sang-Woo Lee1,2, Shin Young Jeong1, Byeong-Cheol Ahn1, Sangil Choi5, In-Kyu Lee2,6, Dong-Kwon Lim7✉, Jaetae Lee1,8✉, Yong Hyun Jeon2,9✉

1. Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea;
2. Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea;
3. Department of Pathology, Chemon Co. Ltd., 240, Nampyeong-Ro, Yangji-Myeon, Cheoin-Gu, Yongin-Si, Gyeonggi-Do, 17162, Republic of Korea;
4. New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea;
5. Department of Pharmacy, School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts, USA;
6. Department of Internal Medicine, Kyungpook National University School of Medicine, Deagu 700-721, South Korea;
7. KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul Anam-ro 145, South Korea;
8. Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea;
9. Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea.
*The first two authors contributed equally to this study.

Abstract

Reliable and sensitive imaging tools are required to track macrophage migration and provide a better understating of their biological roles in various diseases. Here, we demonstrate the possibility of radioactive iodide-embedded gold nanoparticles (RIe-AuNPs) as a cell tracker for nuclear medicine imaging. To demonstrate this utility, we monitored macrophage migration to carrageenan-induced sites of acute inflammation in living subjects and visualized the effects of anti-inflammatory agents on this process. Macrophage labeling with RIe-AuNPs did not alter their biological functions such as cell proliferation, phenotype marker expression, or phagocytic activity. In vivo imaging with positron-emission tomography revealed the migration of labeled macrophages to carrageenan-induced inflammation lesions 3 h after transfer, with highest recruitment at 6 h and a slight decline of radioactive signal at 24 h; these findings were highly consistent with the data of a bio-distribution study. Treatment with dexamethasone (an anti-inflammation drug) or GSK5182 (an ERRγ inverse agonist) hindered macrophage recruitment to the inflamed sites. Our findings suggest that a cell tracking strategy utilizing RIe-AuNPs will likely be highly useful in research related to macrophage-related disease and cell-based therapies.

Keywords: gold nanoparticles, nuclear bio-imaging platform, macrophage migration, acute inflammation.

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How to cite this article:
Lee SB, Lee HW, Singh TD, Li Y, Kim SK, Cho SJ, Lee SW, Jeong SY, Ahn BC, Choi S, Lee IK, Lim DK, Lee J, Jeon YH. Visualization of Macrophage Recruitment to Inflammation Lesions using Highly Sensitive and Stable Radionuclide-Embedded Gold Nanoparticles as a Nuclear Bio-Imaging Platform. Theranostics 2017; 7(4):926-934. doi:10.7150/thno.17131. Available from http://www.thno.org/v07p0926.htm