Study Of ^99mTc-3PRGD₂-SPECT-CT Imaging In Detection Of Neovascularization In Lung Adenocarcinoma

Objective:1.To investigate whether ^99mTC-HYNIC-3PEG4-[c（RGDf K）₂],^99mTc-3PRGD₂-Single Photon Emission Computed Tomography（SPECT）-Computer Tomography（CT）can image lung adenocarcinoma A549 subcutaneous grafts and anti angiogenic lung adenocarcinoma A549 subcutaneous grafts.2.To study the relationship between SPECT-CT imaging intensity and tumor neovascularization,tumor hypoxia,and tumor proliferation in subcutaneously transplanted lung adenocarcinoma A549 cells.3.To study the relationship between SPECT-CT imaging and tumor angiogenesis,tumor hypoxia,and tumor proliferation after subcutaneous transplantation of lung adenocarcinoma A549 cells,in order to further understand the tumor microenvironment.Method:Ten nude mice with lung adenocarcinoma A549 cells were transplanted subcutaneously.Among them,five A549 cells were subcutaneously transplanted tumor mice were treated with cisplatin plus endos tar chemotherapy,and the other five A549 cells were subcutaneously transplanted tumor mice grew normally.The weight of nude mice and the volume of subcutaneously transplanted tumor were measured regularly,and bioluminescence detection was performed.After the end of the chemotherapy cycle,^99mTc-3PRGD₂SPECT/CT was performed to detect the neovascularization of subcutaneously transplanted tumor.After the mice were killed,the subcutaneous metastatic tumor was taken out completely and made into pathological sections.The pathological sections were stained with CD31,Penonazole and EDU immunofluorescence,and the relationship between ^99mTc-3PRGD₂SPECT/CT imaging intensity and tumor microvessel density,tumor hypoxia and tumor proliferation of lung adenocarcinoma A549 cell chemotherapy group and non-chemotherapy group was analyzed.Statistical analysis was carried out using statistical software SPSS 20.0.The data were expressed by mean plus or minus standard deviation,and the relevant indicators of each group were analyzed by Pearson correlation.The difference was statistically significant with P<0.05.Result:1.There was a positive correlation between the T/NT value（1.97±0.24）of^99mTc-3PRGD₂and the number of neovascularization（76.61±2.24）of A549 tumor in chemotherapy group（r=.886,p<0.05）,that is,the higher the T/NT value,the more the number of neovascularization.There was no significant correlation with cell proliferation（1.11±0.22）（r=.426,p>0.05）,and the average fluorescence intensity of hypoxia area（77.49±5.65）（r=-.099,p>0.05）.2.There was a positive correlation between the T/NT value（4.52±0.16）of^99mTc-3PRGD₂and the number of neovascularization（87.10±2.28）of A549 tumor in the non-chemotherapy group（r=.899,p<0.05）,that is,the higher the T/NT value,the more the number of neovascularization.And there was no significant correlation with cell proliferation（1.63±0.34）（r=-.679,p>0.05）,and the average fluorescence intensity of hypoxia area（81.83±6.99）（r=.202,p>0.05）.Conclusion:1.In lung adenocarcinoma A549 chemotherapy group and lung adenocarcinoma A549non-chemotherapy group mice,^99mTc-3PRGD₂-SPECT-CT can effectively image the tumor.2.The T/NT value of ^99mTc-3PRGD₂-SPECT-CT was positively correlated with the density of tumor neovascularization in A549 subcutaneously transplanted tumor in chemotherapy group and A549 subcutaneously transplanted tumor in non-chemotherapy group,but not significantly correlated with the mean fluorescence intensity of tumor hypoxia and cell proliferation rate.