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Abstract
BackgroundWe 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.MethodsForty-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.ResultsAll 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.ConclusionsIn 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 registrationThe 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
Highlights
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
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
Further larger-scale studies are necessary to elucidate the potential role of PIO on 18F-FDG uptake in malignant or inflammatory lesions
Summary
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. Among the synthetic ligands that selectively activate PPAR-γ, thiazolidinedione is an insulin sensitizer that is used to treat hyperglycemia in type 2 diabetes [6, 10]. It reduces insulin resistance in adipose tissue, muscle, and liver [11,12,13,14]. Two types of thiazolidinediones are commercially available in the market, namely troglitazone and pioglitazone (PIO) [15, 16]
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