Correlation between BOLD-MRI and HIF expression level in renal carcinoma

Occupying about 2%~3% of all malignant tumors, renal carcinoma is the most common primary cancer in kidney. The oxidative level of tumor cells is of vital role for optimizing treatment plan, evaluating efficacy and predicting prognosis. This study thus investigated the R2^* value in mouse renal carcinoma model and the correlation between tumor hypoxia and expression level of hypoxia inducible factor-1 (HIF-1). A total of 20 BALB/C nude mice (4~6 weeks old) were inoculated with human ACHN renal carcinoma cells to generate renal cancer model. After the tumor diameter reached 0.5 cm, all animals were examined by BOLD-MRI, both under normal inhalation (R2a^*) and carbogen treatment (R2b^*). The alternation of R2^* values (ΔR2^*=R2a^* - R2b^*) was calculated. Mice were then sacrificed for Immunohistochemical (IHC) staining targeting HIF-1α and HIF-2α. The positive score of HIF was then analyzed for its correlation with R2^* value. In 18 mice finished both experiments, Pearson correlation analysis revealed significant negative correlation between R2a^* and ΔR2^* (r=-0.48, P<0.05) and positive relationship between ΔR2^* and HIF-2α (r=0.38, P<0.05). HIF-1α level, however, did not correlated with tumor R^* values. The positive correlation between ΔR2^* and HIF-2α, but not HIF-1α, suggested potential role of combined BOLD-MRI technique and HIF-1α staining in clinical diagnosis of renal carcinoma. HIF-2α may work as biological marker for renal cancer.