FDG PET reflects aberrant tumor growth in a mouse model for colon carcinoma with enterocyte-specific HIF-1α deficiency

Objectives Tissue specific inactivation of HIF-1α can be used to examine its role in the genesis and progression of various tumors. This approach was used to investigate carcinogenesis of colon cancer in the azoxymethane (AOM)/dextran sodium sulphate (DSS) mouse model with enterocyte-specific HIF-1α deficiency (EHD). In the present study we evaluated FDG PET for the detection and monitoring of differences in tumor metabolism in AOM/DSS mice with and w/o EHD.

Methods FDG PET was performed at 6, 9 and 12wks after AOM injection in 7 EHD and 7 wild-type (WT) mice. For quantification, the maximum FDG uptake in the tumor at 1h p.i. was scaled to the mean uptake in the thigh muscles. The VOIs were placed manually in the PET coregistered to a whole-body CT. Results were correlated with histology, PCR and metabolomics.

Results At 6wks after AOM injection, FDG uptake was significantly lower in the EHD mice than in the WT mice (median uptake 0.7 vs 1.2, Mann-Whitney: p=0.011). At 9 and 12wks, FDG uptake in EHD mice increased to the same level as in WT mice ( 0.8 vs 0.9 at 9wks, p=0.945, and 1.4 vs 1.3 at 12wks, p=0.524, in EHD and WT mice, respectively). These findings were confirmed by non-parametric testing of repeated measures (Friedman test): there was a significant increase of tumor FDG uptake from 6 to 12wks in the EHD mice (p=0.03), but there was no time effect in the WT group (p=0.867). These results are in line with histological and quantitative PCR data which show both a significantly reduced tumor burden and GLUT3 expression in the EHD mice at 6wks but not at later time points. Metabolomic data also revealed significant differences in cellular glucose load between EHD and WT mice at 8wks.

Conclusions Tumor FDG uptake correctly reflected the aberrant time course of glucose metabolism caused by EHD in the AOM/DSS colon carcinoma model. FDG appears to be a useful biomarker for measuring HIF-1α effects in experimental tumor models.