title: The effect of PPAR-γ agonist on (18)F-FDG PET imaging for differentiating tumors and inflammation lesions.
abstract: BACKGROUND
  (18)F-2-deoxy-2-fluoro-d-glucose ((18)F-FDG) positron emission tomography (PET) has been used for imaging human cancers for several decades. Despite its extensive use, (18)F-FDG PET imaging has limitations in the tumor findings. The goal of this study was to investigate the potential of a PPAR-γ agonist pioglitazone (PIO) to distinguish tumors and inflammatory lesions in (18)F-FDG PET imaging.
  
  
  METHODS
  Studies of cellular uptake of (18)F-FDG and Western blot were performed in macrophage (RAW264.7) and three tumor cell lines (A549, KB, and MDA-MB-231) after treatment with PIO. In vivo microPET/CT imaging and biodistribution were performed in animal models.
  
  
  RESULTS
  The uptake of (18)F-FDG in the macrophages was decreased and uptake of (18)F-FDG in the tumor cells was increased when these cells were treated with PIO. Western blot showed that the expression of Glut1 was reduced by treatment of PIO in the macrophage cells, whereas the expression of Glut1 in the tumor cells was increased. In vivo PET/CT imaging revealed that (18)F-FDG uptake (%ID/g) in the tumors was enhanced from 4.05±1.46 to 5.28±1.92 for A549, from 3.9±0.5 to 4.9±0.2 for KB, and from 9.14±0.86 to 13.48±2.07 for MDA-MB-231 tumors after treatment with PIO. Unlike tumors, the RAW264.7 xenograft model showed the reduced (18)F-FDG uptake in the inflammatory lesion from 11.74±1.19 to 6.50±1.47. The results of biodistribution also showed that (18)F-FDG uptake in the tumors were increased after treatment of PIO. However, the uptake of inflammation lesions was reduced.
  
  
  CONCLUSIONS
  In this study, we demonstrated the effect of a PPAR-γ agonist PIO on (18)F-FDG uptake in tumors and inflammation in vitro and in vivo. PIO has potential to differentiate tumors and inflammatory lesions on (18)F-FDG PET imaging.
authors.affiliation: Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Cyclotron Research Center, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Molecular Imaging & Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Cheong
authors.affiliation: Department of Biomedical Engineering, Chonnam National University, Yeosu, Jeonnam 550-749, Republic of Korea.
authors.forename: Chang-Moon
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Cyclotron Research Center, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Molecular Imaging & Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Cyclotron Research Center, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Molecular Imaging & Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea.
authors.forename: Seok Tae
authors.initials: ST
authors.lastname: Lim
authors.affiliation: Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Cyclotron Research Center, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Molecular Imaging & Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Sohn
authors.affiliation: Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Cyclotron Research Center, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Institute for Medical Sciences, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea; Molecular Imaging & Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, 634-18, Geumam-dong, Dukjin-gu, Jeonju, Republic of Korea. Electronic address: jayjeong@jbnu.ac.kr.
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D003937:Diagnosis, Differential; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism / Q000493:pharmacokinetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000037:antagonists & inhibitors; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors; D000077205:Pioglitazone; D049268:Positron-Emission Tomography; D045162:Thiazolidinediones / Q000494:pharmacology*; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D047495:PPAR gamma; D045162:Thiazolidinediones; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D000077205:Pioglitazone
keywords: (18)F-FDG PET; Inflammation; PPAR-γ; Pioglitazone; Tumor