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

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.

In vivo evaluation of the effects of simultaneous inhibition of GLUT-1 and HIF-1α by antisense oligodeoxynucleotides on the radiosensitivity of laryngeal carcinoma using micro 18F-FDG PET/CT

“…Our results were similar to those of other studies in which 18 F-FDG uptake did not correlate with GLUT-1 [43, 44], or HIF-1α expression [45]. However, other studies demonstrated that 18 F-FDG uptake was correlated with HIF-1α [46], and GLUT-1 expression [45].…”

Improving Patient Selection for 18F-FDG PET Scanning in the Staging of Gastric Cancer

“…In gastric cancer, the frequency of GLUT1 expression has been reported to vary between 16.9% and 60% (15-17,31). There have been only a few studies on GLUT1 expression and 18 F-FDG avidity in gastric cancer (15,17,32). Consistent with our current study, Yamada et al reported that GLUT1-positive tumor cells were significantly associated with 18 F-FDG avidity (17).…”

“…However, Takebayashi et al did not find any correlation between the standardized uptake value of primary gastric cancer and GLUT1 expression. Those authors reported hypoxiainducible factor 1a to be another potential clinicopathologic parameter for 18 F-FDG avidity in gastric adenocarcinomas (32).…”

Prospective Evaluation of Changes in Tumor Size and Tumor Metabolism in Patients with Advanced Gastric Cancer Undergoing Chemotherapy: Association and Clinical Implication

“…A study on gastric cancer demonstrated the relationship between T stage and SUV max (15), and another study showed the correlation between the maximal diameter of primary lesion and SUV max . In the latter study, messenger RNA level of hypoxia-inducible factor 1 a was also correlated with SUV max ; therefore, they suggested the mechanism that growth-related hypoxia induces anaerobic glycolysis and increases glucose metabolism (16).…”