Detecting tumor hypoxia level of animals' tumors with SPECT imaging and HIF-1α expression

Objective: To evaluate the feasibility of HIF-1α (hypoxia induce factor-1α) expression and SPECT image with 99Tcm-EC-MNZ (99Tcm-EC-metronidazaole) in detecting tumor hypoxia, and to observe the correlation between these two methods. Methods: After models were set up, 12 Kunming mice bearing S180 sarcoma and 12 C57/BL6 mice bearing Lewis lung cancer were conducted by SPECT image with 99Tcm-EC-MNZ. Then tumor was resected and detected expression of HIF-1α by immunohistochemistry. Results: The T/M ratio of S180 sarcoma 3h after injection of 99Tcm-EC-MNZ ranged from 1.93 to 4.46 (3.04 ± 0.74) and expression of HIF-1α of S180 sarcoma was 31.2%-60.8% (the median: 50.4%). There was significant linear correlation between HIF-1α expression and T/M (t=2.732, P=0.021); The T/M ratio of Lewis lung cancer ranged from 1.42-2.06 (1.78 ± 0.22) and HIF-1α expression of Lewis lung cancer was 0.1%-1.75% (the median: 1.1%). No statistical correlation was observed between the T/M ratio and HIF-1α expression in Lewis cancer (t=1.161, P=0.272). Furthermore, there was significant difference between the T/M ratio of S180 sarcoma and that of lewis lung cancer; the HIF-α expression of S180 sarcoma and that of lewis lung cancer (t'=5.69, P<0.01; t'=0.49, P<0.05). Conclusion: The present results suggest that SPECT image with 99Tcm-EC-MNZ and detection of HIF-1α can predict hypoxic condition in different types of tumor and heterogeneity of hypoxia in the same type of cancer. (authors)