Evaluation of radiosensitivity enhancement by irisquinone with 18F-FETNIM microPET/CT imaging in breast cancer bearing nude mice

Abstract

Objective To investigate the effect of irisquinone (IR) on the radiosensitization of MDA-MB-231 breast cancer in nude mice using 18F-fluoroerythronitroimidazole (18F-FETNIM) microPET/CT. Methods Thirty-two nude mice bearing MDA-MB-231 breast cancer were divided into 4 groups by random number table method (n=8 for each group): group A was treated with radiotherapy alone, group B was treated with radiotherapy and IR, group C was treated with IR alone, and group D was fed with distilled water. 18F-FETNIM microPET/CT images were obtained to monitor the maximum standardized uptake value (SUVmax) of tumor before radiotherapy and 24 h after radiotherapy. The mice were sacrificed and tumor tissues were removed for HE staining. The expression of hypoxia inducible factor-1α (HIF-1α) was detected by immunohistochemical (IHC) method. Data were analyzed by paired t test, one-way analysis of variance, the least significant different t test and Pearson correlation analysis. Results There was no significant difference in SUVmax among the 4 groups before radiotherapy (1.429±0.090, 1.430±0.076, 1.445±0.071, 1.432±0.074; F=0.072, P>0.05). At 24 h after radiotherapy, the SUVmax of group A and B decreased significantly (1.075±0.098, 0.890±0.076; t values: 12.888, 33.217, both P<0.05), and there was significant difference between group B and group A (t=4.197, P<0.05). However, the SUVmax of group C and D increased significantly (1.617±0.090, 1.644±0.063; t values: -11.009, -16.061, both P<0.05). Pathological results showed that tumor cells in group A and B were reduced. IHC results showed that the expression of HIF-1α was lower in group B than others ((26.75±7.19)%; F=46.745, t values: 2.898-9.743, all P<0.05). The expression of HIF-1α was positively correlated with SUVmax (r=0.89, P<0.05). Conclusion 18F-FETNIM microPET/CT could evaluate the radiosensitization effect of IR on MDA-MB-231 breast cancer in nude mice. Key words: Breast neoplasms; Radiation-sensitizing agents; Radiotherapy; Positron-emission tomography; Tomography, X-ray computed; Nitroimidazoles