Study On Integrin Receptor Imaging And Image Texture Prediction Of¹⁸F-Alfatide PET/CT In Esophageal Carcinoma

PET/CT is one of the most advanced nuclear medical imaging techniques,which can analyze the physiological and pathological conditions of normal human tissues,tumors and metastases at the level of molecular metabolism.On this basis,CT can clearly display the tissue structure of various parts of the human body with high resolution,so it can be relatively comprehensive and specific analysis to judge the occurrence,proliferation,invasion and metastasis of tumors.18F-FDG is the most commonly used and mature imaging agent for PET/CT at present.However,some local or systemic infectious foci,non-specific inflammatory tissues and some benign tumors can ingest 18F-FDG in different degrees,which is prone to false positive results and brings significant interference with obvious selectivity and specificity in tumor diagnosis.In addition,obesity,blood glucose level and exogenous insulin have great influence on the distribution of FDG in vivo and imaging,which can affect the accuracy of imaging.Each tracer has different tissue distribution,metabolic processes,and imaging principles in the body,resulting in differences in imaging characteristics and advantages and disadvantages of each tracer Therefore,clinical researchers continue to explore new tracers with higher diagnostic and predictive efficacy.With the continuous development and application of all kinds of new tracers at home and abroad,PET imaging has gradually broken the situation of single application of 18F-FDG.The tumor angiogenesis plays an important role in the tumor growth and metastasis,and can provide a new clue for the diagnosis and treatment of the tumor.Angiogenesis is an important step in the growth and metastasis of the tumor.By the combination of the avp3 and the specific ligand RGD peptide,it is possible to display a tumor tissue with high expression of the ?v?3.which is promising to diagnose the tumor early in the absence of a morphological change in the tumor.A new tracer,18F-AL-NOTA-PRGD2,abbreviated as 18F-alfatide,as a PET/CT tracer,it can be specifically identified and combined with ?v?3.In previous studies,it has confirmed its safety in human body,as well as its value in the diagnosis of lung benign and malignant lesions,which is of good significance for accurate stage and prognosis evaluation of noninvasive lung cancer,and has been successfully visualized in esophageal cancer.The purpose of this study was to explore the value of 18F-Alfatide PET/CT in the diagnosis and clinical application of esophageal cancer.Part one Study on the expression of 18F-Alfatide pet/ct in esophageal carcinoma and its relationship with ?v?3 and VEGF expressionObjectiveThe purpose of this study was to investigate the value of 18F-Alfatide PET/CT in the diagnosis of esophageal cancer and regional lymph node imaging and its diagnostic value,and to study the expression of avp3 and VEGF and microvessel density(MVD)in esophageal cancer tissues by immunohistochemical method and analysis the relationship between them with 8F-Alfatide PET/CT uptake.The relationship between the parameters of 18F-Alfatide PET/CT and the index of tumor invasion and metastasis was studied from the angle of the combination of histology and functional image.MethodsWe selected 49 patients with thoracic esophageal cancer diagnosed pathologically in our hospital were voluntarily admitted to the group and signed informed consent with the approval of Hospital Ethics Committee from September 2015 to July 2018.There was no distant metastasis or definite invasion of adjacent organs in all cases.Esophageal cancer resection and systematic lymph node dissection were performed.The standard uptake value(standard uptake values,SUV)and blood,muscle uptake value the tumor of each patient were recorded separately and the ratio was calculated(tumour-to-blood/muscle ratio).The pathological results were used as the gold standard for diagnosis.Collect the sample of the patient's esophageal cancer and the adjacent tissue of the cancer,record the complete clinical data,and slice the tissue wax block continuously.The expression of integrin avp3,VEGF and MVD in esophageal carcinoma was detected by immunohistochemistry,and the correlation between the results of immunohistochemistry and the uptake value of 18F-Alfatide PET/CT was analyzed.Results1.In 49 patients who completed 18F-Alfatide PET/CT,radical operation was performed in 32 patients with.31 cases of squamous cell carcinoma and 1 case of sarcomatoid carcinoma were diagnosed by histology.All 8F-Alfatide PET/CT patients had no side effects.2.The primary focus of esophageal cancer can be clearly imaging,and the surrounding normal tissue has low radioactivity uptake.The sensitivity,specificity and accuracy of all primary tumors were detected 100%.There were no significant difference in sex distribution between SUVmax,SUVavg and SUVPT/BI,SUVPT/MU in gender,TNM stage and differentiation(p?0.05).3.The 18F-Alfatide PET/CT examination showed that there was a high uptake of 18F-Alfatide in the metastatic lymph nodes of the esophageal carcinoma,while the surrounding normal tissues had lower radioactive uptake.There was no significant difference in the sex distribution of SUVmax-LN,SUVavg-LN,but there was significant difference in the distribution of SUVmax-LN,SUVavg-LN between lymph node metastasis group and non-metastasis group(p?0.01).4.30 patients with esophageal squamous cell carcinoma were performed and their postoperative specimens were immunohistochemical staining,showing that the expression of ?v?3 was mainly expressed in the cell plasma and membrane.Among which 22 cases(73.3%)were positive and 8 cases were negative in tumor tissue,1 case(10.0%)was positive and 9 cases were negative in normal esophageal tissue,the difference was statistically significant(p<0.001).While VEGF mainly expressed in the cytoplasm of cells.Among 30 patients,26 cases(86.67%)were positive for tumor tissue,and 4 cases of negative expression,while 2 cases of positive and 8 cases of negative expression in normal esophageal tissue,the difference was statistically significant(p<0.01).The number of MVD in esophageal carcinoma was significantly increased by CD34 counting,and the positive expression was mainly expressed in small vascular epithelial cells,and the basement membrane of microvascular wall was incomplete and unevenly distributed,especially in stroma and a small amount in cancer nest,with an average value of 21.73 ±5.84.5.The correlation analysis between VEGF and ?v?3 in esophageal carcinoma showed that there was a significant positive correlation between them(r=0.681,p<0.001).The average value of MVD in VEGF positive group was 21.77±6.22,while that in negative group was 16.50±6.76.The results of T-test showed that the MVD value of positive group was higher than that of negative group,but there was no significant difference(p>0.05).The mean value of MVD in the ?v?3 positive group was21.75±6.06,while the mean value of the negative group was 11.5±3.54.The results of T-test between the groups showed that the MVD value of the positive group was significantly higher than that of the negative group(p<0.05).6.The expressions of ?v?3 and VEGF were significantly different in different T stages and N points(P<0.05).The expression levels of ?v?3 and VEGF increased with the increase of T stage,while the expression levels of ?v?3 and VEGF in lymph node metastasis group were significantly higher.In the no lymph node metastasis group(P<0.05).The expression of ?v?3 was significantly correlated with the degree of differentiation(P<0.05).The lower the degree of tumor tissue differentiation,the higher the expression of ?v?3,and the higher the degree of differentiation,the lower the expression of ?v?3.The expression level of ?v?3 increased significantly with clinical stage(P<0.05),and the difference of MVD between different N stages was statistically significant(P<0.05).No significant correlation was found between the other clinical data(P>0.05).7.The SUVmax of ?v?3 positive patients was significantly higher than that of the negative group(P=0.005),and there was a significant positive correlation between them(r=0.545,P=0.002).The SUVmax of VEGF positive patients was higher than that of the negative group(P=0.033).No significant association was found(r=0.128,P=0.499),and there was a significant positive correlation between MVD and SUVmax(r=0.680,P=0.001).Conclusion18F-Alfatide PET/CT can be clearly imaged in esophageal cancer,and has certain value for the diagnosis of esophageal cancer.18F-Alfatide PET/CT can be used to evaluate the blood supply,angiogenesis and distribution of esophageal cancer in esophageal cancer,and to reflect the invasion of esophageal cancer to a certain extent,which is helpful to judge the biological behavior and prognosis of esophageal cancer.Part 2 Comparative study of 18F-Alfatide PET/CT and 18F-FGD PET/CT in esophageal carcinomaObjectiveTo study the difference of the two tracers of 18F-Alfatide PET/CT and 18F-FGD PET/CT in the development of esophageal cancer.Methods61 patients with thoracic esophageal cancer were underwent 18F-Alfatide PET/CT(n=29)and 18F-FDG PET/CT(n=32)scans before surgery within 1 week before operation.The uptake values of tumor and lymph nodes were measured,and the TNM stage was determined by postoperative pathology.The number of cleared lymph nodes and positive lymph nodes was recorded,and the pathological verification was carried out.The position of 18F-Alfatide PET/CT and 18F-FDG PET/CT development and the corresponding uptake value were measured and recorded respectively.Results1.All patients underwent 18F-FDG PET/CT and18F-Alfatide PET/CT with the same esophageal cancer patients,the same lesion on the same level of imaging signs,the two are basically the same.2.The difference of PET/CT uptake value(SUVs)In the 18F-Alfatide PET/CT group,there was no significant difference in the SUV value of primary esophageal cancer in sex(p=0.40),pathological stage(p=0.374),T stage(p=0.205),lymph node status(p=0.744)and differentiation degree(p=0.484),and there was also no significant difference in 18F-FDG PET/CT group(p=0.575,0.81,0.134,0.511 and 0.71,respectively).The SUV values of regional lymph nodes in 18F-Alfatide PET/CT and 18F-FDG PET/CT groups were statistically significant in pathological stage and lymph node status(p=0.003 and 0.001,p=0.002 and<0.001,respectively),but there was no significant difference in sex(p=0.128,0.129),T stage(p=0.791,0.727)and tumor differentiation degree(p=0.049,0.053).3.The correlation between the value of PET/CT and the clinical pathological parametersThere was no significant difference between the primary uptake value of esophageal cancer and lymph node uptake,tumor length,age,sex,pathological stage,T stage,lymph node status and differentiation degree between 8F-Alfatide PET/CT and 8F-FDG PET/CT groups,but there was no significant difference between lymph node uptake value and tumor length,age,sex and t stage.There was a significant positive correlation between lymph node uptake and pathological stage(r=0.52,p=0.016),lymph node metastasis(r=0.73,p<0.001)and differentiation degree(r=0.509,p<0.019),while there was also a positive correlation between lymph node uptake and pathological stage(r=0.503,p<0.01),lymph node metastasis(r=0.649,p<0.001),and differentiation degree(r=0.459,p<0.021),respectively.4.Comparative study on the diagnostic efficacy of two tracers of PET/CT in the diagnosis of regional lymph nodes of esophageal carcinomaA total of 419/95 lymph nodes were removed from the 18F-Alfatide PET/CT group before operation.Among them,49/28 groups were confirmed by histopathology as metastatic lymph nodes.18F-FGD PET/CT examination group was used before operation.A total of 520/106 lymph nodes were removed from the cancer patients,42 of which were confirmed by histopathology as metastatic lymph nodes.The study found that the sensitivity,specificity,accuracy,positive predictive value and negative predictive value of 8F-Alfatide PET/CT,18F-FDG PET/CT esophageal cancer regional lymph node diagnosis were 67.9%VS 82.6%,95.5%VS 85.5%.87.4%VS 84.9%,86.4%VS 61.3%,87.7%VS 94.7%,P values were:0.229,0.043,0.786,0.046,0.747,18F-Alfatide PET/CT specific,positive predictive value higher than 18F-FDG PET/CT was statistically significant(P<0.05).There was no statistical difference between sensitivity,accuracy and negative predictive value(P>0.05).ConclusionsLymph node uptake value SUV-LN is related to pathological stage,lymph node status and differentiation degree,which may be a new parameter of risk stratification in patients with esophageal cancer.18F-Alfatide is a positive diagnostic value with high specificity and positive predictive value for assessing of regional lymph nodes in esophageal cancer.18F-Alfatide PET/CT is a potential alternative to 18F-FDG PET/CT in patients with esophageal cancer.Part three Study on the value of 18F-Alfatide PET/CT texture parameters in predicting the stage and differentiation of esophageal carcinomaObjectivesTo explore the correlation between the structural parameters of PET/CT obtained by 18F-RGD imaging agent and the stage and differentiation degree of esophageal carcinoma.Methods1.72 PET/CT texture parameters obtained by 18F-RGD were ROC analyzed according to the pathological examination results of esophagus cancer patients and the parameters whose area under curve(AUC)above 0.6 were screened out.The correlation between the remain parameters was analyzed and the parameters whose correlation coefficient with others was above 0.8 were screened.2.The correlation of the remain parameters and TNM stage was analyzed.The differences of every parameters between early stage group and late stage group were compared and Logistic regression analysis was conducted to analyze the correlation of parameters and stage.3.The remain parameters were ROC analyzed according to the T stage,N stage and differentiation degree respectively and the parameters whose AUC was above 0.6 were screened out and the classfication cut-off value were computed.Results1.Tumor volume(TV),maximum SUV(SUVMa)and low-intensity zone emphasis(LIZE)were correlated with TNM stage;TV,SUVMa,contrast of cooccurance(Con_C),LIZE and high-intensity large-zone emphasis(HILZE)were correlated with early or late stage,in which SUVMa and Con C were independent correlation factors;2.TV,SUVMa,mean SUV(SUVMe),SUV skewness(SUVSk),Con_C,homogeneity of cooccurance(Hom_C),contrast of neighborhood intensity difference(Con_Ne),black-white symmetry(Sym),size-zone variability(SZV),LIZE,low-intensity large-zone emphasis(LILZE),HILZE were correlated with T stage3.TV,SUVMa,SUVMe,SUVSk,Con C and Hom_C were correlated with N stage4.SUV Kurtosis,Cor C were correlated with differentiation degree.ConclusionsPET/CT texture parameters of esophagus cancer were well obtained by 18F-Alfatide maging agent,and multiple parameters have diagnostic value on stage and differentiation degree of esophagus cancer.