| Objective:Lung cancer is one of the malignancies with a relatively high mortality rate in the world.One of the main factors affecting the prognosis of lung cancer is local invasion and metastasis..Integrins play an important role in the metastasis of lung cancer.The accuracy of 99mTc-3p RGD2 was verified by being able to visualize and semi-quantitatively analyze the changes in RGD uptake at different periods of tumor growth in a lung cancer tumor model constructed from lung cancer tumor cells with different invasive metastatic capabilities in vivo that can reflect integrin levels,and compared with immunohistochemical histochemistry results to explore the role of99mTc-3p RGD2 in predicting local tumor invasion and metastatic potential.Method:Tumor cells of A549 and H460 were selected for subcutaneous tumor modeling in nude mice.Tumor formation occurred in 21 nude mice of the A549 group and 15 nude mice of the H460 group.After the tumor formation in the first week,the second weeks and the sixth weeks,we test the rat by using 99mTc-3 prgd2SPECT/CT imaging,and observe the tumor imaging agent intakes.The semi-quantitative method is used to analyze the image results,remove the tumor tissue after each imaging,tumor diameter and measured with vernier caliper for alpha v beta 3,CD31 and ki67 immunohistochemical examination,and semi-quantitative analysis by software.Results:The adhesion of the tumor to surrounding tissue was more obvious in group A549 than in group H460,and no distant metastasis was found in both groups.1.Comparison of tumor diameter changes over time between group A549 and group H460 Tumor diameters at 1,2 and 6 weeks in A549 group were 0.99±0.07 cm,1.26±0.05 cm and 1.71±0.09 cm,while those in H460 group were 1.30±0.08 cm,2.06±0.21 cm and 2.96±0..11 cm.The difference of tumor diameter between the two groups at the 1st,2nd and 6th week was statistically significant（P<0.05）2.Comparison of 99mTc-3PRGD2 imaging with the time between A549 group and H460 group RGD SPECT imaging showed obvious uptake of liver and spleen imaging agents in group A549 and group H460,and tumors located in the right axilla of nude mice were developed.The T/NT ratios of the A549 group at 1,2 and 6 weeks were 1.76±0.11,2.34±0.39 and 3.38±0.29.The T/NT ratio of the H460 group at 1,2 and 6 weeks were1.55±0.15,2.12±0.16 and 1.72±0.12.There were statistically significant differences in the T/NT ratio between the A549 group and H460 group at weeks 1 and 6（P<0.05）,and there was no significant difference in the T/NT ratio at the second week（P<0.05）.3.Comparison of immunohistochemical and semi-quantitative analysis results over time between group A549 and group H4603.1 Integrin immunohistochemical smears showed deep staining of the tumor and vascular cell cytoplasm and capsule.The surface densities of the A549 group at weeks1,2 and 6 were calculated as 1.89±0.20,2.61±0.21 and 3.72±0.15.The surface density of group H460 at weeks 1,2 and 6 was 1.69±0.09,2.28±0.26 and 1.79±0.14.The difference in surface density between group A549 and group H460 at weeks 2and 6 were statistically significant（P>0.05）,and there was no statistical significance in the first week（P<0.05）.3.2 The CD31 immunohistochemical smear showed dark brown staining of vascular endothelial cells.The average vascular density of the A549 group at weeks 1,2 and 6was 361.05±15.33 /mm2,376.73±14.78 /mm2 and 403.38±21.71 /mm2.The average vascular density of the H460 group at the 1st,2nd and 6th weeks was 267.92±32.90 vessels /mm2,270.66±28.57 vessels /mm2 and 391.36±46.34 vessels /mm2.The difference of average vessel density between the A549 group and H460 group at the first and second week was statistically significant（P<0.05）,the difference was not statistically significant at the 6th week（P>0.05）. 3.3 Ki67 immunohistochemical smears showed that the nuclei of positive cells were dark brown,and the positive cell rates were 2.85±0.24%,2.34±0.38% and2.28±0.20% at the first,second and sixth weeks of A549.The positive cell rate of H460 at weeks 1,2 and 6 was 4.88±0.31%,1.70±0.34% and 0.79±0.10%.The positive cell rate of the A549 group and H460 group was significantly different at the1 st,2nd and 6th week（P<0.05）.4.Comparison of T/NT values,tumor diameter and immunohistochemical changes over time between A549 group and H460 group The variation trend of T/NT values in the A549 and H460 groups was similar to the variation trend of integrin expression intensity over time.The expression of H460 integrin,which showed strong proliferative ability in the early period of cellular growth,was not high.It can be seen that the expression intensity of integrin in the A549 group had the same trend as that of microvessel density.However,the expression intensity of H460 synthins and the changing trend of microvascular density were the same in the 1st to 2nd week and different in the 2nd to 6th week.Conclusion: In vivo dynamic 99mTc-3PRGD2 imaging and semi-quantitative analysis can reflect the expression of integrin between different tumor cells at different stages of tumor growth.In vivo RGD imaging may indicate the possibility of local invasion or even metastasis of tumor. |
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