Establishment And Imaging Study Of Rabbit Lung VX2 Cancer Model

[Purpose] Imaging examination is the important method for lung cancer diagnosis and its follow-up therapeutic effect. The research of lung cancer needs suitable animal model. This study is through the method to investigate and establish rabbit lung VX2 transplanted tumor model, the method is to puncture VX2 lung tumor tissue masses into pulmonary parenchyma under the guidance of computer tomography (CT). Meanwhile using the common method as the control which is to eject VX2 lung tumor tissue suspensions under the guidance of CT, establish a rabbit lung VX2 transplanted tumor model suitable for imaging experiment and study, and observe the VX2 lung transplanted tumor biological characteristics by CT scanning. Rabbit lung VX2 transplanted tumor model is treated using the short-time big-dosage radiation therapy, and initially investigate 18F-FDG PET imaging characteristics before and after radiation therapy for rabbit lung VX2 transplanted tumor models.[Methods]1. The establishment of rabbit lung VX2 transplanted tumor model30 New Zealand rabbits are randomly divided into experiment group and control group, respectively using the methods which are to eject VX2 tumor tissue masses and tumor tissue suspensions under the guidance of CT to establish animal models, every group is 15 rabbits. Experiment group is to eject VX2 tumor tissue masses under the guidance of CT, control group is to eject tumor tissue suspensions under the guidance of CT, compare the implanted achievement ratio of two methods, implantation ratio of pleura and chest wall, the size and metastasis of tumor, and analyze the life span difference of two groups.2. Imaging evaluation of rabbit lung VX2 transplanted tumor10 days after implantation rabbit lungs are plain scanned and enhancement scanned by spiral computer tomography every 3 days. Observe visibility rate of lung transplanted tumor, metastasis and natural growth state. For experiment rabbits which have beared tumor using LungCARE software in Siemens sensation 64 spiral CT, definite the authenticity of nodus and precisely determine the content and density of lung nodus, observe three dimensional structure of lung nodus and its relationship with adjacent blood vessel and bronchi. Calculate doubling time and growth rate of VX2 lung nodus.3,Evaluate the induction radiotherapy effect of rabbit lung VX2 transplanted tumor using 18F-FDG PET12 New Zealand rabbits which successfully have been implanted lung VX2 transplanted tumor, are treated using the short-time big-dose radiation therapy (once a day, for two consecutive days, total dose is 30 Gy, equivalent to accumulative conventional expose dose 62.5 Gy). The seventh day before and after radiation therapy 18F-FDG PET scans the rabbit lungs, PET imaging is performed at 1h (early) and 2h (delayed) after injection, Semi-quantitative analysis is performed using the standardised uptake value (SUV). Using 18F-FDG concentrated percent change of lung transplanted tumor before and after radiation therapy evaluates the SUV change of rabbit lung VX2 transplanted tumor. The rabbits are executed, and then the histopathological analysis of tumor specimens are obtained through surgery.[Result]1. Establishment of rabbit lung VX2 transplanted tumor model: 13 rabbits are implanted successfully in experiment group, the achievement ratio is 86.7%(13/15), the rate of the chest seeding is 40%(6/15), the mean survival time is 58±6 days. 15 rabbits in control group are all implanted successfully, the achievement ratio is 100%(15/15), the rate of the chest seeding is 86.7% (13/15), the mean survival time is 29±7days. The life span of two groups are analyzed by Kaplan-Meier curve, the results show the life span of two groups are significantly different (P<0.001), the life span of experiment group is significantly higher than that of control group. Implantation ratio of pleura and chest wall, the achievement ratio of tumor implantation are analyzed by chi-square test. Implantation ratio of pleura and chest wall of experiment group is lower than that of control group (P<0.05), there is statistical significance. The achievement ratio of tumor implantation doesn't have statistical significance (P>0.05). Implantation ratio of pleura and chest wall directly influences the life span.2. Imaging evaluation of rabbit lung VX2 transplanted tumor: 10~20 days after tumor implantation, CT plain scan is performed, don't appear right lung tumor nodus, imaging appearance is similar round or little Irregular shape density shadow of soft tissue in lung, the clear boundary, more even density in focus of infection.Tumor nodus of this stage are about 0.5~1cm, these CT value are 98.25±16.77HU, see short burr in lung window, don't have significant sublobe, arterial phase is significantly unevenly enhanced when enhancement scan is performed, the enhancement CT value are 138.61±28.70HU. 20~30 days after tumor implantation, the nodus gradually grow up, because the content of rabbit thoracic cavity is limited, so the nodus involve adjacent pleura, the tumor nodus significantly increase, appear pleural effusion, tumor density gradually unevenly decrease, limbic density is little higher, there is lower necrotic focus in low density focus, it appears circinate enhancement after been enhanced scanning, there is no significant enhancement in central necrotic focus. >30 days the tumor grows up quickly, the boundary with adjacent chest wall, diaphragma and right heart isn't clear, the enhancement scanning characteristics of pleura, chest wall and mediastinum's metastasis are similar with that of the main focus. At the tenth, thirteenth, sixteenth, nineteenth day, the volumes of lung nodus respectively is 70.88±26.46mm3, 110.54±34.30mm3, 163.75±56.92mm3 and 293.22±119.97mm3, the doubling time is 6.80±2.78 days, which is consistent with the feature of malignant tumor.3. 18F-FDG PET imaging study of rabbit lung VX2 transplanted tumor before and after radiation therapy: PET imaging is performed at the first time, results show the SUVmax1h of tumor is 2.95±1.04, the SUVmax2h is 3.58±1.32. 7 days after radiation therapy PET imaging is performed, the SUVmax1h of tumor is 1.47±0.36, the SUVmax2h is 1.88±0.44. After radiation therapy, PET imaging is performed at 1h (early) after injection, 18F-FDG concentrated percent change decreases to 60.48±5.66, PET imaging is performed at 2h (delayed) after injection, 18F-FDG concentrated percent change decreases to 57.18±6.79. Before and after radiation therapy PET imaging is performed at 1h (early) after injection, the SUVs of rabbit lung VX2 transplanted tumor are analyzed by t-test. Before and after radiation therapy PET imaging is performed at 2h (delayed) after injection, the SUVs are analyzed by t-test. Results show there are significant differences in SUV before and after radiation therapy (p<0.05).[Conclusion]1.Comparing with the group which is to eject tumor tissue suspensions into pulmonary parenchyma under the guidance of CT, the group which is to eject tumor tissue masses into pulmonary parenchyma would form single nodule in lung, significantly decrease implantation ratio of pleura and chest wall, and thereby increase live time of animals. This method has the advantages, such as easy cope, short growth cycle of animals, high achievement ratio of implantation, stable and so on, it is suitable for imaging study.2. LungCARE software can show the three dimensional structure of rabbit lung VX2 transplanted tumor, the relationship between lung nodus and adjacent blood vessel and bronchi, and can precisely determine the content of nodus. This method is better than the method which is to determine the two-dimensional structure, diameter, area and volume of rabbit lung VX2 transplanted tumor. Through calculate the doubling time and growth rate of VX2 lung nodus, help us better understand the bionomics of rabbit lung VX2 transplanted tumor.3. After radiation therapy 18F-FDG PET imaging is performed for rabbit lung VX2 transplanted tumor model, the SUVs significantly decrease, that can early evaluate the reaction of rabbit lung VX2 transplanted tumor for radiation therapy before VX2 transplanted tumor occurs morphology change.