Alteration of hypoxia and glucose metabolism measured by 18F-FMISO and 18F-FDG MicroPET/CT imaging during anti-angiogenic therapy

Objectives Anti-angiogenic therapy (AAT) is now widely-used clinic anticancer strategy by blocking the oxygen and nutrient supply to starve cancer cells. Herein, we aimed to measure the alteration of hypoxia and glucose metabolism by 18F-FMISO and 18F-FDG MicroPET/CT imaging during AAT and to establish a potential molecular imaging strategy to monitor early response.

Methods U87MG tumor models in nude mice were randomly separated into two treatment and control groups. The treatment groups were intragastrically injected with Sunitinib at the dose of 80 mg/kg for 7 consecutive days and the control ones with vehicle. 18F-FMISO and 18F-FDG imaging were acquired by MicroPET/CT scanner at day 0, 1, 3, 7 and 13 after AAT. The mean Standardized Uptake Values (SUVmean) in the regions of interest (ROI) of tumor were applied for the quantitative analysis. The tumor tissues were collected to perform the immunohistochemical analysis of HIF-1α, Glut-1 and CD31 staining. Data were expressed as mean±SD and analyzed using One-Way ANOVA test and Pearson correlation analysis.

Results Alteration of hypoxia and glucose metabolism during AAT was found by longitudinal 18F-FMISO and 18F-FDG MicroPET/CT imaging (Figure 1). The tumor uptake of 18F-FMISO in the Sunitinib group decreased significantly at day 3 post AAT, comparing with that in vehicle one, and the SUVmean was 0.535±0.031 vs 0.728±0.062 (P=0.004). The corresponding HIF-1α level was also significantly different between both groups (18.2±2.1% vs 27.5±5.0%, P=0.013). However, there were no significant changes for 18F-FDG uptakes and Glut-1 expression between AAT and control groups. Moreover, AAT efficiency was confirmed by CD31 staining, which showed tumor microvessel density in therapy group lowered significantly than that in control one from day 1 to 7 post AAT.

Conclusions Significant alteration of hypoxia level during AAT was successfully measured by 18F-FMISO MicroPET/CT imaging which might be a more potential molecular imaging strategy to monitor early response to AAT than18F-FDG.

Research Support This study was partly supported by National Natural Science Foundation of China (No. 11275050, No. 30700188).