Antitumor Effects Of ¹²⁵I Seeds Brachytherapy On Nude Mice With Human Fibrosarcoma

The soft tissue sarcoma has low incidence rate, but does a great harm to health of the people. At present, surgical operation is a main procedure which is often combined with radiotherapy and chemotherapy to improve therapeutic efficacy. The tumor is charactered with higher rate of local recurrence and lower rate of local control. So the medical workers are looking for novel therapeutic methods all the time. Recently, radiotherapy is limited, because cure dosage of external irradiation is very higher than tolerance dosage of normal tissue around. Interstitial implantation of radioactive seeds, one kind of brachytherapy, is a good method which can greatly injury tumor by implanting radioactive microsources which can irradiate garmmer rays with low capacity continuously whereas normal tissue is not or slightly injuried.¹²⁵I is the most common radioactive seed nowadays,which is used especially in the treatment of prostate cancer, pancreatic carcinoma, hepatocarcinoma and cancer of head and cervix. ¹²⁵I should be considered that different activity, dose or distribution of the seed can make different effectiveness. Thus, it is of great practical value that the effective radioactive of ¹²⁵I seeds with different activity on therapy for fibrosarcoma was evaluated. We studied on it through animal experiment. At the same time, the radiation damage of radioactive ¹²⁵I seeds was explored preliminarily.Objective: To investigate the effect of different activities of ¹²⁵I radioactive seed implantation for nude mice with transplanted human tumor cancer of the fibrosarcoma.Methods: We gained The Human fibrosarcoma cells (HT-1080) by culture , subculture and collection in vitro . After adjusting the cell density to 5×10⁷ L-1, 200μL of them were inoculated into the nude mice When the subcutaneous implanted tumor was grown to (5±1)mm, Tumor biopsies were resected and cutted into a small cubes. Then implanted them into healthy nude mice.32 Animal models simulating human fibrosarcoma were established by subcutaneous implantation of HT-1080 cell lines into nude mice. Mice were randomly divided into treated group and control group. The treated group was implanted with different activity of ¹²⁵I seed: low-activity group(14.8MBq, n=8),moderate-activity group(22.2MBq n=8) and high-activity group(29.6MBq, n=8).While the control group (n=8) was implanted with the dummy seed. Regularly observed the nude mice'tumar and evaluated by caliper measurements, The longest is a, the shortest is b. The tumorous'volume(mm3)were calculated according to formula V=ab2×0.52.Transplantion tumor growth curve was drawing according to zhe formula calculate. General cases and survival rates of nude mice were observed at the same time. At the time of 15th day, the tumor was cut off. The tumor inhibition ratio(IR)=(Control group–Treated group) the average tumor volume/the mean control group's tumor volume. And the tumor IR was Compared in different groups. Based on Radiation Therapy Oncology Group (RTOG)[1] acute radiation injury standard, region skin reaction were evaluated. The histopathologic change was assessed according to the Rectal Cancer Regression Grade (RCRG) system of Wheeler[2]. Analysis of variance and Kruskal-Wallis H test were employed to deal with the experimental data respectively with the statistic softwares by SAS 8.1.Results:Every group of nude mice were maintained normal on water drinking, food intake, urine and feces before and after the ¹²⁵I seeds implantation. Nude mice in control group had less subcutaneous fat than treated group. The survival ratio rate in control group , low , moderate and high activity groups were 75.0%, 83.3%,100% and 100% respectively. The growth curve of turmor volume was drawing. The figure of the control group presented more rapid rising than the low-activity group. While the moderate-activity group and high-activity group show an downward tendency. The growth inhibitory rates in low-activity group, moderate-activity group and high-activity group were separate 32.06%,84.28% and 90.43%. Between there was significant difference (P<0.05). Based on RTOG[1] acute radiation injury standard, the results are: There were no acute radiation injury in the control group and the low-activity group . 2 nude mice in moderate-activity group presented grade 1. In high-activity group, 3 nude mice presented grade 1, 2 nude mice presented grade 4. There was no significant difference in regional skin reaction between control groups and low-activity groups(P>0.05), and there was significant difference between control group and moderate, high-activity group(P<0.05), and between moderate and high-activity groups(P<0.05). According to the RCRG system of Wheeler[2] the extent of pathological response raised up followed by increasing activity. The pathological response in the control group was all RCRG 3; 4 were RCRG 3 and 4 were RCRG 2 in moderate-activity group; 5 were RCRG 1 and 3 were RCRG 2 in high-activity group. There was significant difference between control and different activity groups (P<0.05), except for difference between moderate group and high activity group (P>0.05).Conclusions: Interstitial implantation with ¹²⁵I seeds had significant inhibitory sarcoma effect on the human fibrosarcoma xenografts in nude mice, and the activity of the seed can affect treatment effectiveness and the extent of radiation injury. Moderate activity (22.2MBq) of ¹²⁵I seeds implantation rates maybe a better choice from growth inhibitory and regional skin injury.