Evaluating Changes of Tumor Hypoxia Using 99Tcm-MNLS Hypoxic Imaging

Abstract

Background: Hypoxia is an important cause of recurrence and metastasis of malignant tumors. Noninvasive detection of the extent of hypoxic areas of tumors is essential for delineation of radiotherapy target areas and dose. Objectives: To investigate the feasibility of 99 Tc m-2-(2-methyl-5-nitro-1H-imidazol-1-yl) ethyl dihydrogen phosphate (99 Tc m-MNLS) hypoxic imaging to monitor the tumor hypoxic state in tumor-bearing mice after radiotherapy. Materials and Methods: Tumor-bearing mice were divided into eight groups: imaged 24 hours before radiotherapy (A24 h before), imaged immediately after radiotherapy (Aimmediately), imaged 24 hours after radiotherapy (A24 h), imaged 48 hours after radiotherapy (A48 h), and the corresponding control groups. Mice in each group received hypoxia imaging at the corresponding time point to calculate the radioactivity ratio of tumor/non-tumor (T/NT). Hypoxia inducible factor-1α (HIF-1α) was determined by immunohistochemistry to investigate the relationship between T/NT ratio and HIF-1α expression in radiotherapy and control groups. Results: T/NT ratio and the expression of HIF-1α in A24 h group were not significantly different from those in A24 h before and control groups, but lower than those in the Aimmediately group and higher than those in the A48 h group. T/NT ratio and the expression of HIF-1α in the A24 h before group had no significant difference compared with those in its control group, while those in the Aimmediately group were remarkably higher than those in its control group. On the other hand, those in A48 h group were lower than those in its control group. There was a positive correlation between T/NT ratio and HIF-1α expression in radiotherapy group and control group at different time points. Conclusion: 99 Tc m-MNLS tumor hypoxic imaging can evaluate the tumor hypoxic status of tumor-bearing mice after radiotherapy.