title: Combined Fluorescence and Magnetic Resonance Imaging of Primary Macrophage Migration to Sites of Acute Inflammation Using Near-Infrared Fluorescent Magnetic Nanoparticles.
abstract: OBJECTIVE
  This study aimed to track the migration of primary macrophages labeled with near-infrared (NIR) fluorescent magnetic nanoparticles toward chemically induced acute inflammatory lesions in mice and to visualize the effect of anti-inflammatory drugs on macrophage migration using combined fluorescence and magnetic resonance imaging (FLI/MRI).
  
  
  METHODS
  Primary macrophages were labeled with NIR fluorescent magnetic nanoparticles, and labeled cells were injected into mice intravenously. One day later, inflammation was induced by subcutaneous injection of 1% carrageenan (CG) solution to footpads of the right hind leg, and phosphate-buffered saline (PBS) as control treatment was subcutaneously injected to footpad of the left hind leg. To evaluate the effect of drug treatment on macrophage migration, a single dose of dexamethasone (DEX) was intraperitoneally administered to the mice immediately after the induction of inflammation and was followed by combined FLI/MRI at predetermined time points.
  
  
  RESULTS
  No difference in cellular viability or phagocytic activity was observed between the labeled and parent macrophages. In vivo optical imaging revealed an increase in FLI signals in CG-injected footpads in a time-dependent manner, but not in PBS-treated footpads. DEX treatment inhibited the migration of the labeled macrophages to the CG-injected footpads, with relative decreases in FLI activity. In accordance with FLI, T2*-weighted MR images showed hypo-intense signals in the CG-injected footpads but not in the PBS-injected footpads. The DEX-treated mice did not show a dark signal loss zone on MR images in the CG-treated paw.
  
  
  CONCLUSIONS
  We successfully tracked the migration of macrophages to inflammatory lesions using both FLI and MRI with NIR fluorescent magnetic nanoparticles and demonstrated the inhibitory effects of DEX on macrophage migration to inflammation sites.
authors: Department of Nuclear Medicine, Catholic University of Daegu School of Medicine, Gyeongsan-si, South Korea.
authors: Sungmin
authors: S
authors: Kang
authors: Department of Nuclear Medicine, Kyungpook National University School of Medicine, 50 Samduk-dong 2-ga, Chung Gu, Daegu, 700-721, South Korea.
authors: Ho Won
authors: HW
authors: Lee
authors: Department of Nuclear Medicine, Kyungpook National University School of Medicine, 50 Samduk-dong 2-ga, Chung Gu, Daegu, 700-721, South Korea. jeon9014@gmail.com.|Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, 807 Hogukro, Bukgu, Daegu, 702-210, South Korea. jeon9014@gmail.com.
authors: Young Hyun
authors: YH
authors: Jeon
authors: Department of Nuclear Medicine, Kyungpook National University School of Medicine, 50 Samduk-dong 2-ga, Chung Gu, Daegu, 700-721, South Korea.
authors: Thoudam Debraj
authors: TD
authors: Singh
authors: Department of Nuclear Medicine, Kyungpook National University School of Medicine, 50 Samduk-dong 2-ga, Chung Gu, Daegu, 700-721, South Korea.
authors: Yun Ju
authors: YJ
authors: Choi
authors: Department of Pathology, Kyungpook National University School of Medicine, Daegu, South Korea.
authors: Ji Young
authors: JY
authors: Park
authors: R&D Center, Biterials, Goyang-si, 410-050, South Korea.
authors: Jun Sung
authors: JS
authors: Kim
authors: Division of MR Research, Korea Basic Science Institute, Daejeon, South Korea.
authors: Hyunseung
authors: H
authors: Lee
authors: Division of MR Research, Korea Basic Science Institute, Daejeon, South Korea.
authors: Kwan Soo
authors: KS
authors: Hong
authors: Department of Endocrinology, Kyungpook National University School of Medicine, Daegu, South Korea.
authors: Inkyu
authors: I
authors: Lee
authors: Department of Nuclear Medicine, Kyungpook National University School of Medicine, 50 Samduk-dong 2-ga, Chung Gu, Daegu, 700-721, South Korea.
authors: Shin Young
authors: SY
authors: Jeong
authors: Department of Nuclear Medicine, Kyungpook National University School of Medicine, 50 Samduk-dong 2-ga, Chung Gu, Daegu, 700-721, South Korea.
authors: Sang-Woo
authors: SW
authors: Lee
authors: Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, South Korea.
authors: Jeoung-Hee
authors: JH
authors: Ha
authors: Department of Nuclear Medicine, Kyungpook National University School of Medicine, 50 Samduk-dong 2-ga, Chung Gu, Daegu, 700-721, South Korea.
authors: Byeong-Cheol
authors: BC
authors: Ahn
authors: Department of Nuclear Medicine, Kyungpook National University School of Medicine, 50 Samduk-dong 2-ga, Chung Gu, Daegu, 700-721, South Korea. jaetae@knu.ac.kr.|Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Cheombok-ro, Dong-gu, Daegu, 701-310, Korea. jaetae@knu.ac.kr.
authors: Jaetae
authors: J
authors: Lee
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D002470:Cell Survival; D005456:Fluorescent Dyes; D007249:Inflammation / Q000276:immunology*; D008264:Macrophages / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods*; D013050:Spectrometry, Fluorescence / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles
keywords: Acute inflammation; Combined fluorescence and magnetic resonance imaging; Macrophage migration; Near-infrared fluorescent magnetic nanoparticles