18F]Fluorodeoxyglucose accumulation as a biological marker of hypoxic status but not glucose transport ability in gastric cancer

Ryusuke Takebayashi,Yasuyuki Suzuki,Tsutomu Masaki,Kunihiko Izuishi,Hirohito Mori,Reiko Kameyama,Yuka Yamamoto

doi:10.1186/1756-9966-32-34

Abstract

BackgroundThe use of [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for detection of gastric cancer is often debated because FDG uptake varies for each patient. The purpose of this study was to clarify the molecular mechanisms involved in FDG uptake.Material and methodsFifty patients with gastric cancer who underwent FDG-PET and gastrectomy were studied. Snap-frozen tumor specimens were collected and examined by real-time PCR for relationships between maximum standardized uptake value (SUV) and mRNA expression of the following genes: glucose transporter 1 (GLUT1), hexokinase 2 (HK2), hypoxia-inducible factor 1α (HIF1α), and proliferating cell nuclear antigen (PCNA).ResultsTumor size was the only clinicopathological parameter that significantly correlated with SUV. Transcripts for the genes evaluated were about three-fold higher in malignant specimens than in normal mucosa, although only HIF1α was significantly correlated with SUV. When divided into intestinal and non-intestinal tumors, there was a significant correlation between SUV and tumor size in intestinal tumors. Interestingly, the weak association between SUV and HIF1α expression in intestinal tumors was substantially stronger in non-intestinal tumors. No correlation was found between SUV and mRNA expression of other genes in intestinal or non-intestinal tumors.ConclusionSUV was correlated with HIF1α, but not PCNA, HK2, or GLUT1 expression. FDG accumulation could therefore represent tissue hypoxia rather than glucose transport activity for aggressive cancer growth.

Highlights

The use of [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for detection of gastric cancer is often debated because FDG uptake varies for each patient
Transcripts for the genes evaluated were about three-fold higher in malignant specimens than in normal mucosa, only hypoxia-inducible factor 1α (HIF1α) was significantly correlated with standardized uptake value (SUV)
Ott et al found that a reduction in FDG uptake of more than 35% for metabolic responders predicted a favorable response in gastric cancer patients two weeks after initiation of chemotherapy [11], while metabolic non-responders or FDG non-avid tumors received an unfavorable prognosis

Summary

Introduction

The use of [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for detection of gastric cancer is often debated because FDG uptake varies for each patient. Radiology examinations provide important information for cancer treatment, and [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) differs from conventional imaging through its use of cellular metabolic characteristics to detect a variety of tumors and metastases [1,2]. Besides detecting tumors based on absolute value, FDG-PET can assess the response to chemotherapy based on relative values before and after cancer treatment [1]. A correlation between FDG uptake and GLUT1 expression has been found in gastric cancer patients [1,3,7,8], but these studies were conducted by non-quantitative immunohistochemistry analysis, such as negative or positive staining that can vary by evaluator. We discuss the significance and difficulties involved with the clinical application of FDG-PET in gastric cancer due to FDG uptake mechanisms

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