title: Visualization of Macrophage Recruitment to Inflammation Lesions using Highly Sensitive and Stable Radionuclide-Embedded Gold Nanoparticles as a Nuclear Bio-Imaging Platform.
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 vivoimaging 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.
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea;; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Sang Bong
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Ho Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Thoudam Debraj
authors.initials: TD
authors.lastname: Singh
authors.affiliation: Department of Pathology, Chemon Co. Ltd., 240, Nampyeong-Ro, Yangji-Myeon, Cheoin-Gu, Yongin-Si, Gyeonggi-Do, 17162, Republic of Korea.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea.
authors.forename: Sang Kyoon
authors.initials: SK
authors.lastname: Kim
authors.affiliation: New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea;; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Ahn
authors.affiliation: Department of Pharmacy, School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts, USA.
authors.forename: Sangil
authors.initials: S
authors.lastname: Choi
authors.affiliation: Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea;; Department of Internal Medicine, Kyungpook National University School of Medicine, Deagu 700-721, South Korea.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
authors.affiliation: KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul Anam-ro 145, South Korea.
authors.forename: Dong-Kwon
authors.initials: DK
authors.lastname: Lim
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea;; Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea.
authors.forename: Jaetae
authors.initials: J
authors.lastname: Lee
authors.affiliation: Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea;; Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea.
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Jeon
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002351:Carrageenan / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004195:Disease Models, Animal; D006046:Gold / Q000032:analysis*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D007457:Iodine Radioisotopes / Q000032:analysis*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D053758:Nanoparticles / Q000032:analysis*; D049268:Positron-Emission Tomography / Q000379:methods*; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000893:Anti-Inflammatory Agents; C583041:GSK5182; D007457:Iodine Radioisotopes; D013629:Tamoxifen; D006046:Gold; D003907:Dexamethasone; D002351:Carrageenan
keywords: acute inflammation.; gold nanoparticles; macrophage migration; nuclear bio-imaging platform