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EJNMMI Research
Published in: EJNMMI Research 1/2015

Open Access 01-12-2015 | Original research

A phase II clinical trial to investigate the effect of pioglitazone on 18F-FDG uptake in malignant lesions

Authors: Yeon-Hee Han, Seong Young Kwon, Jeonghun Kim, Chang Ju Na, Sehun Choi, Jung-Joon Min, Hee-Seung Bom, Young-Chul Kim, In-Jae Oh, Han-Jung Chae, Seok Tae Lim, Myung-Hee Sohn, Hwan-Jeong Jeong

Published in: EJNMMI Research | Issue 1/2015

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Abstract

Background

We found that 18F-2-fluoro-2-deoxy-D-glucose (18F-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 18F-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, 18F-FDG PET/CT images were acquired from patients without administration of pioglitazone (PIO), which is a PPAR-γ agonist. On the next day, 18F-FDG PET/CT images were acquired once again from the same patients after administration of PIO. We measured the 18F-FDG uptake in malignant lesions or inflammatory lesions from two 18F-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 18F-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 18F-FDG uptake in malignant or inflammatory lesions.

Trial registration

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
Literature
1.
Kota BP, Huang TH, Roufoqalis BD. An overview on biological mechanisms of PPARs. Pharmacol Res. 2005;51:85–94.CrossRefPubMed
2.
Berger JP, Akiyama TE, Meinke PT. PPARs: therapeutic targets for metabolic disease. Trends Pharmacol Sci. 2005;26:244–51.CrossRefPubMed
3.
4.
Schoonjans K, Staels B, Auwerx J. The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta. 1996;1302:93–109.CrossRefPubMed
5.
Fruchart JC, Duriez P, Staels B. Peroxisome proliferator-activated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis. Curr Opin Lipidol. 1999;10:245–57.CrossRefPubMed
6.
Michalik L, Auwerx J, Berger JP, Chatterjee VK, Glass CK, Gonzalez FJ, et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activator receptors. Pharmacol Rev. 2006;58:726–41.CrossRefPubMed
7.
Cunard R, Ricote M, DiCampli D, Archer DC, Kahn DA, Glass CK, et al. Regulation of cytokine expression by ligands of peroxisome proliferator activated receptors. J Immunol. 2002;168:2795–802.CrossRefPubMed
8.
9.
Kieć-Wilk B, Dembińska-Kieć A, Olszanecka A, Bodzioch M, Kawecka-Jaszcz K. The selected pathophysiological aspects of PPARs activation. J Physiol Pharmacol. 2005;56:149–62.PubMed
10.
Fürnsinn C, Waldhäusl W. Thiazolidinediones: metabolic actions in vitro. Diabetologia. 2002;45:1211–23.CrossRefPubMed
11.
Oakes ND, Camilleri S, Furler SM, Chisholm DJ, Kraegen EW. The insulin sensitizer, BRL 49653, reduces systemic fatty acid supply and utilization and tissue lipid availability in the rat. Metabolism. 1997;46:935–42.CrossRefPubMed
12.
Young PW, Cawthorne MA, Coyle PJ, et al. Repeat treatment of obese mice with BRL 49653, a new potent insulin sensitizer, enhances insulin action in white adipocytes. Association with increased insulin binding and cell-surface GLUT4 as measured by photoaffinity labeling. Diabetes. 1995;44:1087–92.CrossRefPubMed
13.
Oakes ND, Kennedy CJ, Jenkins AB, Laybutt DR, Chisholm DJ, Kraegen EW. A new antidiabetic agent, BRL 49653, reduces lipid availability and improves insulin action and glucoregulation in the rat. Diabetes. 1994;43:1203–10.CrossRefPubMed
14.
Smith SA, Lister CA, Toseland CD, Buckingham RE. Rosiglitazone prevents the onset of hyperglycaemia and proteinuria in the Zucker diabetic fatty rat. Diabetes Obes Metab. 2000;2:363–72.CrossRefPubMed
15.
Sakamoto J, Kimura H, Moriyama S, Odaka H, Momose Y, Sugiyama Y, et al. Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone. Biochem Biophys Res Commun. 2000;278:704–11.CrossRefPubMed
16.
Kudzma DJ. Effects of thiazolidinediones for early treatment of type 2 diabetes mellitus. Am J Manag Care. 2002;8:472–82.
17.
Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature. 1998;391:82–6.CrossRefPubMed
18.
Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator activated receptor-gamma is a negative regulator of macrophage activation. Nature. 1998;391:79–82.CrossRefPubMed
19.
Straus DS, Glass CK. Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms. Trends Immunol. 2007;28:551–8.CrossRefPubMed
20.
Kapucu LO, Meltzer CC, Townsend DW, Keenan RJ, Luketich JD. Fluorine-18-fluorodeoxyglucose uptake in pneumonia. J Nucl Med. 1998;39:1267–9.PubMed
21.
Goo JM, Im JG, Do KH, Yeo JS, Seo JB, Kim HY, et al. Pulmonary tuberculoma evaluated by means of FDG PET: findings in 10 cases. Radiology. 2000;216:117–21.CrossRefPubMed
22.
Demura Y, Tsuchida T, Ishizaki T, Mizuno S, Totani Y, Ameshima S, et al. 18F-FDG accumulation with PET for differentiation between benign and malignant lesions in the thorax. J Nucl Med. 2003;44:540–8.PubMed
23.
Nishiyama Y, Yamamoto Y, Fukunaga K, Kimura N, Miki A, Sasakawa Y, et al. Dual-time-point 18F-FDG PET for the evaluation of gallbladder carcinoma. J Nucl Med. 2006;47:633–8.PubMed
24.
Gamelli RL, Liu H, He LK, Hofmann CA. Augmentations of glucose uptake and glucose transporter-1 in macrophages following thermal injury and sepsis in mice. J Leukoc Biol. 1996;59:639–47.PubMed
25.
Kim SL, Kim EM, Cheong SJ, Lee CM, Kim DW, Jeong HJ. The effect of PPAR-γ agonist on 18F-FDG uptake in tumor and macrophages and tumor cells. Nucl Med Biol. 2009;36:427–33.CrossRefPubMed
26.
Cheong SJ, Lee CM, Kim EM, Lim ST, Sohn MH, Jeong HJ. The effect of PPAR-γ agonist on 18F-FDG PET imaging for differentiating tumors and inflammation lesions. Nucl Med Biol. 2015;42:85–91.CrossRefPubMed
27.
Hauner H. The mode of action of thiazolidinediones. Diabetes Metab Res REV. 2002;18:10–5.CrossRef
28.
Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457–71.CrossRefPubMed
29.
Breunig IM, Shaya FT, McPherson ML, Snitker S. Development of heart failure in medicaid patients with type 2 diabetes treated with pioglitazone, rosiglitazone, or metformin. J Manag Care Pharm. 2014;20:895–903.
30.
Hiatt WR, Kaul S, Smith RJ. The cardiovascular safety of diabetes drugs--insights from the rosiglitazone experience. N Engl J Med. 2013;369:1285–7.CrossRefPubMed
31.
Aspinall SE, Zhao X, Good CB, Stone RA, Smith KJ, Cunningham FE. FDA warning and removal of rosiglitazone from VA national formulary. Am J Manag Care. 2013;19:748–58.PubMed
32.
Fukumura D, Jain RK. Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize. J Cell Biochem. 2007;101:937–49.CrossRefPubMed
33.
Kubota R, Kubota K, Yamada S, Tada M, Ido T, Tamahashi N. Microautoradiographic study for the differentiation of intratumoral macrophages, granulation tissues and cancer cells by the dynamics of fluorine-18-fluorodeoxyglucose uptake. J Nucl Med. 1994;35:104–12.PubMed
34.
Kang SR, Song HC, Byun BH, Oh JR, Kim HS, Hong SP, et al. Intratumoral metabolic heterogeneity for prediction of disease progression after concurrent chemoradiotherapy in patients with inoperable stage III non-small-cell lung cancer. Nucl Med Mol Imaging. 2014;48:16–25.PubMedCentralCrossRefPubMed
35.
Budiawan H, Cheon GJ, Im HJ, Lee SJ, Paeng JC, Kang KW, et al. Heterogeneity analysis of 18F-FDG uptake in differentiating between metastatic and inflammatory lymph nodes in adenocarcinoma of the lung: comparison with other parameters and its application in a clinical setting. Nucl Med Mol Imaging. 2013;47:232–41.PubMedCentralCrossRefPubMed
Metadata
Title
A phase II clinical trial to investigate the effect of pioglitazone on 18F-FDG uptake in malignant lesions
Authors
Yeon-Hee Han
Seong Young Kwon
Jeonghun Kim
Chang Ju Na
Sehun Choi
Jung-Joon Min
Hee-Seung Bom
Young-Chul Kim
In-Jae Oh
Han-Jung Chae
Seok Tae Lim
Myung-Hee Sohn
Hwan-Jeong Jeong
Publication date
01-12-2015
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2015
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-015-0128-9

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