Correlation Between ^99mTc-3PRGD₂ SPECT/CT Imaging And Expression Of Integrin ?v?3 In Non-small Cell Lung Cancer

Objective:In this study,56 patients with clinically highly suspected lung cancer were examined by ^99mTc-3PRGD₂ SPECT/CT imaging,and the expression level of integrin?v?3 in all postoperative pathological specimens was detected by immunohistochemical SP technique.?1?The value of T/N ratio of ^99mTc-3PRGD₂ SPECT/CT imaging in the diagnosis of lung cancer was discussed.?2?The expression level of integrin?v?3 in pathological specimens of patients with benign and malignant lung cancer was analyzed.?3?The correlation between T/N ratio and?v?3 expression in benign and malignant lesions was explored.Methods:Retrospectively collected imaging data of 56 patients who underwent ^99mTc-3PRGD₂ SPECT/CT imaging in our department from July 2015 to December 2016 and performed surgery within 7 days after imaging,and 93 postoperative pathological blocks was collected at last.The patients were divided into malignant lesion group and benign lesion group according to the gold standard of pathological diagnosis after operation.The ROI is delineated on the SPECT/CT imaging and the ratio of the tumor's highest uptake value?T?to the contralateral normal lung tissue uptake value?N?is calculated as the ratio of T/N.?1?The ROC curve was drawn according to T/N ratio of benign and malignant lesions.The optimal threshold of ^99mTc-3PRGD₂ SPECT/CT imaging lesion's T/N for judging benign and malignant lesions was calculated by calculating the area under the curve.And the diagnostic efficiency of ^99mTc-3PRGD₂ imaging's T/N ratio for lung cancer was calculated.?2?The expression level of integrin?v?3 in lung lesions and normal tissue adjacent to tumors was detected by immunohistochemical SP method.The expression levels of integrin?v?3 in non-small cell lung cancer?NSCLC?,benign lung lesions and normal tissues adjacent to tumors were analyzed.The correlation between T/N ratio,tumor size and integrin?v?3 expression in NSCLC was investigated.Statistical analysis was performed by SPSS 22.0.The t test was used for comparison between the two groups.One-way analysis of variance was used for comparison between groups.P<0.05 was considered statistically significant.The relationship between the expression level of integrin?v?3 and the T/N ratio of NSCLC and ^99mTc-3PRGD₂ SPECT/CT imaging was analyzed by Spearman correlation analysis.The relationship between integrin?v?3level and tumor diameter was analyzed by Pearson correlation analysis.And our research was approved by the Hospital Ethics Committee.Results:1.The T/N ratio of ^99mTc-3PRGD₂ SPECT/CT imaging between benign and malignant lesions was significant difference,T=-2.070,P=0.043<0.05.There was no significant difference in T/N ratio between lung adenocarcinoma and squamous cell carcinoma,pneumonia lesions and other benign lesions,T=-0.431 and 1.01,respectively,P>0.05.2.The ROC curve was drawn according to the T/N ratio of the two groups of patients with malignant lung lesions and benign lesions.The optimal threshold value of T/N ratio was calculated.The area under the ROC curve was 0.682?P=0.035<0.05?,and ROC analysis suggested an T/N cut-off value of 2.07 to differentiate between malignant lesions and benign lesions.At this time,the sensitivity,specificity,accuracy,positive predictive value?PPV?and negative predictive value?NPV?of^99mTc-3PRGD₂ SPECT/CT in the diagnosis of patients with malignant lung disease were 77.50%,56.25%,71.4%,81.58%and 50.00%,respectively.3.Immunohistochemistry results showed that there were 30 positive expressions of integrin?v?3 in 36 NSCLC pathological blocks,the positive rate was 83.3%.Weak positive,medium positive and strong positive accounted for26.7%,46.7%and 26.6%respectively.Integrin?v?3 mainly expressed in the cell membrane and cytoplasm of tumor cells and macrophages in lesions.There were 8 positive expressions of integrin?v?3 in the pathological block of 14 benign lesions,the positive rate was 57.1%.There was no strong positive expression,while the weak positive and medium positive expression accounted for 62.5%and 37.5%respectively.Integrin?v?3 also was concentrated in the cell membrane and cytoplasm of macrophages.There were 14 positive expressions of integrin?v?3in the pathological block of 43 normal tissues adjacent to tumors,the positive rate was 57.1%and all integrin?v?3 expression was weak positive.The expression of integrin?v?3 was concentrated in the cell membrane and cytoplasm of macrophages in lesion either.Integrin?v?3expression was not observed in normal alveolar and interstitial lung.The expression of integrin?v?3 in malignant lung lesion group,benign lung lesion group and adjacent normal tissues adjacent to tumors had significant difference,X²=34.237,P=0.000<0.05.There was no significant difference in the expression of integrin?v?3 between benign lesions and normal tissues adjacent to tumors.4.Immunohistochemistry results showed that the expression of integrin?v?3 was highly correlated with NSCLC?R=0.606,P=0.000<0.05?.5.The T/N ratio which can judge the benign and malignant lesions by NSCLC ^99mTc-3PRGD₂ SPECT/CT imaging has a medium correlation with the intensity of immunohistochemistry?R=0.423,P=0.002<0.05?but a weak correlation with tumor's diameter?R=0.378,P=0.002<0.05?.Conclusion:1.The T/N ratio of ^99mTc-3PRGD₂ SPECT/CT imaging between benign and malignant lesions was significant difference.The sensitivity,specificity,accuracy,positive predictive value?PPV?and negative predictive value?NPV?of ^99mTc-3PRGD₂ SPECT/CT in the diagnosis of patients with malignant lung disease were 77.50%,56.25%,71.4%,81.58%and50.00%,respectively.2.Immunohistochemical results showed that there was a statistically significant difference in the level of integrin?v?3 expression between NSCLC,benign lesions and normal tissues.The expression of integrin?v?3 in NSCLC group is mainly concentrated in the cell membrane and cytoplasm of macrophages in tumor cells and tumor cells.Integrin?v?3 in benign lesions and normal tissues adjacent to the tumor mainly accumulate in the cell membrane and cytoplasm of scattered macrophages.3.The expression of integrin?v?3 was highly correlated with NSCLC?R=0.606,P=0.000<0.05?.The T/N ratio of NSCLC has a medium correlation with the intensity of immunohistochemistry?R=0.423,P=0.002<0.05?but a weak correlation with tumor's diameter?R=0.378,P=0.002<0.05?.4.The expression of integrin?v?3 in the cell membrane and cytoplasm of macrophages may be the cause of false positive of ^99mTc-3PRGD₂ SPECT/CT imaging.^99mTc-3PRGD₂SPECT/CT imaging has limited value in the diagnosis of lesions less than 1.5cm in diameter.