title: A phase II clinical trial to investigate the effect of pioglitazone on (18)F-FDG uptake in malignant lesions.
abstract: BACKGROUND
  We found that (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) uptake in malignant lesion was enhanced, and it was decreased in the inflammatory lesion after the use of peroxisome proliferator activated receptor-γ (PPAR-γ) agonist in our previous preclinical study. The purpose of this study was to investigate the effect of PPAR-γ agonist on malignant lesions in clinical (18)F-FDG positron emission tomography/computed tomography (PET/CT) imaging.
  
  
  METHODS
  Forty-three patients were enrolled in this prospective study. We received the approval for the investigator-initiated trials for a phase II human clinical trial from the Korean Food and Drug Administration. On the first day, (18)F-FDG PET/CT images were acquired from patients without administration of pioglitazone (PIO), which is a PPAR-γ agonist. On the next day, (18)F-FDG PET/CT images were acquired once again from the same patients after administration of PIO. We measured the (18)F-FDG uptake in malignant lesions or inflammatory lesions from two (18)F-FDG PET/CT images. Four different PET parameters were used to compare between the two studies: SUVmax, SUVmean, average activity over 30 % of the isocontour (isocontour, Bq/mL), and isocontour-mediastinal activity (Bq/mL). Additionally, we classified the patients into two groups: the responder or non-responder group according to the presence of PIO effect on skeletal muscle. Furthermore, PET parameters of malignant lesions were analyzed based on the type of malignancy and were compared with those of inflammatory lesions.
  
  
  RESULTS
  All four PET parameters of malignant lesions in the responder group showed increasing patterns after the use of PIO. In the subgroup analysis, the similar pattern was observed in gastrointestinal cancer. In hepatobiliary and pancreatic cancer, SUVmean and isocontour showed statistically significant increase in the presence of PIO. On the other hand, in the non-responder group, all four PET parameters showed decreasing patterns in both malignant and inflammatory lesions after the use of PIO. There was no statistically significant difference in PET parameters of malignant lesions in the non-responder group.
  
  
  CONCLUSIONS
  In this study, we found that PIO had the potential to increase (18)F-FDG uptake of malignant lesions in the patients who showed PIO effect on skeletal muscle. Contrary to our preclinical studies, clinical results had limitations to evaluate malignant lesions in non-responder group. Further larger-scale studies are necessary to elucidate the potential role of PIO on (18)F-FDG uptake in malignant or inflammatory lesions.
  
  
  BACKGROUND
  The test for safety and effectiveness of the new efficacy of Pioglitazone to diagnose the malignant tumor and inflammation in F-18 FDG positron emission tomography (PET) study, 12029.
authors.affiliation: Department of Nuclear Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Cyclotron Research Center, Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea. yani0878@hanmail.net.
authors.forename: Yeon-Hee
authors.initials: YH
authors.lastname: Han
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeonnam, Republic of Korea. suninocean@hanmail.net.
authors.forename: Seong Young
authors.initials: SY
authors.lastname: Kwon
authors.affiliation: Department of Nuclear Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Cyclotron Research Center, Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea. cruivy43@naver.com.
authors.forename: Jeonghun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Cyclotron Research Center, Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea. ncj29@naver.com.
authors.forename: Chang Ju
authors.initials: CJ
authors.lastname: Na
authors.affiliation: Department of Nuclear Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Cyclotron Research Center, Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea. cshever@hanmail.net.
authors.forename: Sehun
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeonnam, Republic of Korea. jjmin@jnu.ac.kr.
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Min
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeonnam, Republic of Korea. hsbom@jnm.ac.kr.
authors.forename: Hee-Seung
authors.initials: HS
authors.lastname: Bom
authors.affiliation: Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeonnam, Republic of Korea. kyc0923@chonnam.ac.kr.
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Hwasun-gun, Jeonnam, Republic of Korea. droij@jnu.ac.kr.
authors.forename: In-Jae
authors.initials: IJ
authors.lastname: Oh
authors.affiliation: Department of Pharmacology, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea. hjchae@jbnu.ac.kr.
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Chae
authors.affiliation: Department of Nuclear Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Cyclotron Research Center, Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea. stlim@jbnu.ac.kr.
authors.forename: Seok Tae
authors.initials: ST
authors.lastname: Lim
authors.affiliation: Department of Nuclear Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Cyclotron Research Center, Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea. mhsohn@jbnu.ac.kr.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Sohn
authors.affiliation: Department of Nuclear Medicine, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Cyclotron Research Center, Molecular Imaging and Therapeutic Medicine Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, Republic of Korea. jayjeong@chonbuk.ac.kr.
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
keywords: 18F-FDG uptake; Inflammatory lesion; Malignant lesion; PPAR-γ pioglitazone