| Lung cancer is a common malignant tumor, which is on the top of the mortality rate among all tumors. In the recent 50 years, the incidence of lung cancer increased significantly all over the world. Statistics show that the incidence of lung cancer has been on top of all other tumors of male in some big cities of both china and other countries in Europe and America. As a result of smoking and various of environmental factors, the incidence and mortality rate of lung cancer are rising rapidly around the world in recent years, particularly in industrial countries.The method of 125I particles interstitial brachytherapy to tumor is a low-dose-rate but continuing ionizing radiation treatment. This method is widely used to treat the tumor because it is merits of effective on the tumor destruction, small damage to surrounding normal tissue, simple operation and light trauma. However, there are few researches about the particle activity and the total dose of the particle of treatment. As a matter of fact, the relationship among the prescription dose, the actual dose of target volume obtained and the dose of tumor eradication is still unclear. Also, few research about tumor recurrence after this kind of treatment have been reported. In this study, a research has done in this context.Objective: Through animal experiments , the relationship between prescription dose and the actual cumulative dose of the target area are studied. Aslo the inhibitory effect of the radioactive particles on tumor growth is observed, and the efficacy of radioactive particles inhibit tumor recurrence is cleared. It hopes that some theoretical supports can be given to clinical work. Methods:This experimentation is divided into two parts.Part 1: The tissue actual cumulative dose should be carried out. 60 healthy C57BL/6J mice are randomly divided into two groups. Different activity particles(0.5mCi and 0.8mCi)are implanted in the subcutaneous tissue in mice armpit. Thermo luminescent dosimeter (TLD) is laid 0.5cm away from the particles in the subcutaneous tissue in mice armpit. Six mice are randomly sampled at 3rd days, 6th days, 9th days, 12th days, and 15th days. The TLD will be measured by HeBei province CDC. The cumulative curve about the tissue actual cumulative dose with time is described by software. Find the time when the tissue cumulative dose reached 5Gy and 10Gy, then compared them with the theoretical value time which got from AAPM formula calculated.Part 2: The effect of 125I particles inhibiting tumor tissue should be observed. 48 healthy C57BL/6J mice are randomly divided into two groups: 0.5mCi group and 0.8mCi group, each group is divided into a control group and an experiment group. 0.2ml Lewis lung cancer single cell suspension (5×106) is implanted in subcutaneous of mice armpit, at the same time, 0.5 (0.8 or empty) mCi125I particles is implanted 0.5cm away from the cells implantation point. Six mice are randomly sampling each group when the day we got from the first part when the tissue cumulative dose reached 5Gy and 10Gy, then tumor size is measured, tumor inhibition rate is calculated. Samping at 0.5cm away from particle, the change of tumor histomorphology by microtome section of pathology is observed; apoptosis rate is analyzed by Tunel, apoptotic index is calculated.Results:1 The tissue'cumulative dose: The 0.5mCi group tissue'cumulative dose of 3th d, 6th d, 9th d, 12th d 15th d which is measured by TLD are 130.4±8.8, 264.4±18.1, 391.6±20.1, 518.1±27.1, 669.2±32.4. The 0.8mCi group tissue'cumulative dose of 3th d, 6th d, 9th d, 12th d 15th d which is measured by TLD are 212.8±10.3,407±18.7,608.3±24.2,814.5±34.5,1002.2±66. 5. Then it's fitted curve with the date.2 The day when the tissue'cumulative dose reached 5Gy, 10Gy: According to measurements and fitting curves, we can calculate the day when the tissue 0.5cm away from 0.5mCi particle cumulative dose reached 5Gy, 10Gy is 11th d, 24.5th d respectively, and the day the day when the tissue 0.5cm away from 0.8mCi particle cumulative dose reached 5Gy, 10Gy is 7th d, 14.5th d respectively. Calculated according to AAPM formula the day when the tissue 0.5cm away from 0.5mCi particle cumulative dose reached 5Gy, 10Gy is 10.1th d, 21.6th d respectively, and the day when the tissue 0.5cm away from 0.8mCi particle cumulative dose reached 5Gy, 10Gy is 6.2th d, 12.9th d respectively.3 Change of tumor size: Control group:Mice are planted with tumor cells , miliary sized tumor nodules can be touched in the local subcutaneous at the 4-6th day; tumor nodules'diameter reached 1.0cm at the 10-14th day later; the tumor packaged the forelimb of the mouse at the 19th day later, and it is difficult for the mice to walk. The 0.5mCi radioactive particles experiment group: There are no tumor nodules that can be touched at the 6th day. Tumor nodules can be touched under the local subcutaneous at the 10th day, and diameter reached 0.6cm at the 15th day. Compared with the control group, the tumor is significant smaller. Radioactive particle have significant effect for inhibit tumorigenesis in mice. The 0.8mCi radioactive particles experiment group: There are no tumor nodules that can be touched at the 6th day. Tumor nodules can be touched under the local subcutaneous at the 10th day, and diameter reached 0.3cm at the 15th day. Compared with the control group, the tumor is significant smaller.4 Inhibition rate: The wight of 5Gy, 10Gy in 0.5mCi group is: 0.65±0.24g, 0.98±0.35g, inhibition rate is 72.34%, 85.43%, which is statistically significant (P<0.05); the wight of 5Gy, 10Gy in 0.5mCi group is: 0.52±0.15g, 0.62±0.26g, inhibition rate is 75.39%, 87.03%, which is statistically significant (P<0.05). The inhibition rate has significant difference. In two experiment groups under the same radiation dose, inhibition rate had no significant difference in statistics (P> 0.05).5 Expression on morphology (light microscope) Control group: It can be seen a wide range of inflammatory cell infiltrated in the tumor tissue,and a rare of apoptosis cell expressed. Experiment group: A wide range of inflammatory cell infiltration, massive apoptosis, which manifested as nuclear membrane shrinkage, condensed nuclei, chromatin crescent integrated condensate, and some fragmentate,and form of apoptotic bodies, which cytoplasmic vacuoles increased was seen in tumor tissue.6 Tunel staining: The nuclei of Positive cells are marked brown yellow or brown. In addition to nuclear condensation, labeled cells nuclear fragmentation is found, and some of nucleus without obvious condensation is also found, while few of apoptotic cells appeared in the control group. In the experimental group, apoptotic rate is higher than the control group, and there is statistically significant (P <0.01), so radioactive particles can cause an increase in apoptosis.Conclusion:1 Tissue actual cumulative dose is below the AAPM prescription dose.2 Mice are treated by 125I brachytherapy, and tumorigenesis could be inhibited tumor growth; as time prolonged, particles activity increased, the effect of inhibit tumor growth improved.3 Pathology results: necrosis existed at the sites of tumor, apoptosis could be found around necrosis. The tumor is inhibited growth because the radiation causes apoptosis of tumor after implantation.4 Tunel staining confirmed apoptosis of tumor cells after particle irradiation 125I particles can effectively inhibit tumor value from proliferating and growing.
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