The effectiveness of gefitinib combined with ¹²⁵I radioactive particles for the treatment of pulmonary adenocarcinoma:an experimental study in nude mice

Objective: To investigate the efficacy of gefitinib combined with ¹²⁵I radioactive particles in the treatment of transplantation tumor of lung cancer cell line A549 in nude mice. Methods: A total of 24 nude mice models were established by using human lung adenocarcinoma cells with stable expression of luciferase A549-luc. The tumor size was about 8-10 mm at 20 days after implantation of tumor cells. The mice were randomly and equally divided into blank control group (n = 6), ¹²⁵I seed implantation group (n = 6), gefitinib group (n = 6) and gefitinib plus ¹²⁵I seed implantation group (combination group, n = 6). The growth of the tumors was under close observation, and the change of tumor size was continuously measured. Bioluminescence imaging was used to detect the bioluminescence activity of human lung adenocarcinoma A549-luc cells containing the luciferase reporter gene in vivo. 18 F-FDG MicroPET/CT was performed before and one week after treatment. The experimental mice were sacrificed at 35 days after treatment, and the tumor growth curve was drawn. Results No statistically significant difference in preoperative tumor volume existed between each other among the four groups. Five weeks after treatment, the tumor volumes of the control group, ¹²⁵I seed implantation group, gefitinib groups and combination group were (1509.25 ± 709.93) mm³, (840.45 ± 43.35)mm³, (1052.96 ± 247.42) mm³ and (317.34 ± 52.08) mm³ respectively. There was significant difference in tumor volume between the combination group and each of the other three groups (F = 10.305, P < 0.05). The tumor volume in the combination group was significantly smaller than that in other three groups, and also it was remarkably smaller than its preoperative one. Before treatment there was no significant difference in the bioluminescence signal intensity between each other among the four groups. Four weeks after treatment, the biofluorescence photons of the control group, ^125I seed implantation group, gefitinib groups and combination group were (198605000.0 ± 12976503.00), (99263333.33 ± 49293480.57), (87419500.0 ± 24039740.21) and (48433333.33 ± 14417910.62) P/sec/cm²/sr respectively, the difference between each other among the four groups was statistically significant (F = 28.975, P < 0.05). The biofluorescence photons of the combination group was strikingly lower than that of other three groups, and it also was remarkably lower than its preoperative one. No statistically significant differences in preoperative SUV_max and SUV_mean values existed between each other of the four groups. One week after treatment, the SUV_max and SUV_mean values in the control group, ¹²⁵I seed implantation group, gefitinib groups and combination group were (0.79 ± 0.14) and (0.54 ± 0.06), (0.76 ± 0.33) and (0.47 ± 0.41), (0.79 ± 0.15) and (0.48 ± 0.11), (0.74 ± 0.14) and (0.57 ± 0.74) respectively, the differences in SUV_max and SUV_mean values between each other among the four groups were not statistically significant (F = 0.201, P > 0.05). Conclusion: Gefitinib combined with ¹²⁵I radioactive particles brachytherapy can significantly inhibit tumor growth. (authors)