The Value Of ^99mTc-Galacto-RGD₂SPECT/CT Imaging In The Diagnosis And Staging Of Cervical Cancer

Part I Bio-distribution of ^99mTc-Galacto-RGD₂ in human bodyObjectives: To discuss the bio-distribution of ^99mTc-Galacto-RGD₂ in human body and the using safety by determining the average radioactive count of ^99mTc-Galacto-RGD₂ in important organs of human body and by calculating radioactive count ratio of important organ tissue/muscle?T/M?,important organ tissue/blood ratio?T/B?,and comparativing analysis of the bio-distribution of 18F-FDG in organismMethod: This study was approved by the Ethics Committee of Affiliated Hospital of Chuanbei Medical College.Forty patients with suspected cervical cancer based on disease history,clinical symptoms and auxiliary examinations like CT,MRI or ultrasound from September 2014 to October 2014 were included,averagely aged 49.6±10.5 years old?27 70 years old?.^99mTc-Galacto-RGD₂ whole body imaging,18F-FDG whole body imaging were carried out among all patients.Images were read and analyzed.^99mTc-Galacto-RGD₂ and 18F-FDG radioactive uptake value of important organ tissues were recorded and important organ tissue and muscle?T/M: target/muscle?ratio and important organ tissue and blood ratio?T/B: target/blood?were calculated.Data analysis was carried out using SPSS19.0 software.Single sample Kolmogorov-Smirnov was used to test the normal distribution condition of the data and comparison of mean and standard deviation.Column diagram and percentage constituent ratio of important organs were drawn.Result:1.^99mTc-Galacto-RGD₂ has a good bio-distribution feature,mainly distributed in the urinary system and the digestive system;the radioactive uptake in important organ tissues including brain,heart,muscle and lung is low and the image is clearer.2.The radioactive count of ^99mTc-Galacto-RGD₂ in the bladder is the highest?3061.27±2068.96?;secondly kidney?1074.86±870.92?and the radioactive uptake in organs including spleen,livers,colon,stomach,pancreas and rectum is relatively high.The radioactive uptake in important organs including muscle,lung,jejuno-ileum,vertebra and blood is relatively low and the radioactive uptake in the brain tissue is the lowest?20.36±5.16?.3.The radioactive uptake of 18F-FDG in the bladder is the highest?3330.25±166.90?,secondly brain?3330.25±166.90?,the radioactive uptake of 18F-FDG in the liver,spleen,stomach,colon,esophagus and rectum is relatively high,the radioactive uptake of thyroid,kidney,blood and muscle is relatively low and the radioactive uptake of lungs is the lowest?369.50±29.90?.Conclusion:1.^99mTc-Galacto-RGD₂ is of high safety and has a good bio-distribution feature.2.^99mTc-Galacto-RGD₂ is mainly excreted from the urinary system and metabolized from livers;the radioactive uptake of muscle,lung and heart is relatively lower and the radioactive uptake of brain tissue is the lowest.Part II Contrastive analysis of ^99mTc-Galacto-RGD₂ and 18F-FDG wholebody imaging in the diagnosis of cervical cancerObjectives: To compare the image quality of ^99mTc-Galacto-RGD₂ and 18F-FDG and their value in monitoring cervical cancer primary lesion,lymph node metastasis condition and clinical staging and to discuss the diagnosis efficiency of ^99mTc-Galacto-RGD₂ in diagnosing primary lesion of cervical cancer,detecting pelvic lymph node metastasis and clinical preoperative staging,so as to provide SPECT/CT or PET/CT imaging agent with better or equivalent to 18F-FDG in clinical diagnosis of cervical cancer.Method: The research objects are the same with that in the first part.Forty patients with suspected cervical cancer based on disease history,clinical symptoms,physical examinations and auxiliary examinations like CT,MRI or ultrasound?with cervical biopsy tissue or postoperative pathological examination results as the final diagnosis evidence?underwent ^99mTc-Galacto-RGD₂ whole body imaging and 18F-FDG whole body imaging.^99mTc-Galacto-RGD₂ and 18F-FDG images were obtained and delivered to two associate professors or professors in nuclear medicine,who would read images,determine the radioactive count ratio?T/NT?of three sites of cervical tumor/muscle and analyze the value of ^99mTc-Galacto-RGD₂ and 18F-FDG images in diagnosing primary lesion of cervical cancer,detecting pelvic lymph node metastasis and accurate preoperative clinical staging.Data processing was carried out by using SPSS19.0 statistical software.The measurement materials adopted mean value±standard deviation.The enumeration data was shown in frequency.Paired t test was adopted for intra-group comparison.Enumeration data was tested by adopting chi-square test or paired chi-square test.P<0.05 was considered to be statistically significant.Result:1.T/NT of ^99mTc-Galacto-RGD₂ and 18F-FDG in the tissue of cervical cancer was 5.68±1.87,2.67±0.96,and there was a significant difference?P<0.001?,that is,T/NT value of ^99mTc-Galacto-RGD₂ in the cervical cancer tissue was higher than T/NT value of 18F-FDG.T/NT of ^99mTc-Galacto-RGD₂ and 18F-FDG in the tissue of cervical benign lesions was 3.32±0.46,1.49±0.21,and there was a significant difference?P=0.000?,that is,T/NT value of ^99mTc-Galacto-RGD₂ in the cervical benign lesions tissue was higher than T/NT value of 18F-FDG.2.The sensitivity of ^99mTc-Galacto-RGD₂ diagnosing cervical cancer primary lesion was 88.24%?30/34?,the specificity was 66.67%?4/6?,the positive predicating value was 93.75%?30/32?,the negative predicating value was 50.00%?4/8?and the accuracy rate was 85.00%?34/40?.The sensitivity of 18F-FDG diagnosing cervical cancer was 85.29%?29/34?,the specificity was 83.33%?5/6?,the positive predicating value was 96.67%?29/30?,the negative predicating value was 50.00%?5/10?and the accuracy rate was 85.00%?34/40?.The difference between them in sensitivity,specificity,accuracy rate,positive predicating value and negative predicating value had no statistical significance,that is,^99mTc-Galacto-RGD₂ imaging had a similar efficiency with 18F-FDG in diagnosing primary lesion of cervical cancer.3.The sensitivity of ^99mTc-Galacto-RGD₂ diagnosing pelvic lymph node metastasis was 75.00%?6/8?,the specificity was 88.46%?23/26?,the positive predicating value was 66.67%?6/9?,the negative predicating value was 92.00%?23/25?and the accuracy rate was 85.29%?29/34?.The sensitivity of 18F-FDG diagnosing pelvic lymph node metastasis was 62.50%?5/8?,the specificity was 88.46%?23/26?,the positive predicating value was 62.50%?5/8?,the negative predicating value was 88.46%?23/26?and the accuracy rate was 82.35%?28/34?.The difference between them in sensitivity,specificity,accuracy rate,positive predicating value and negative predicating value had no statistical significance,that is,^99mTc-Galacto-RGD₂ imaging had a similar efficiency with 18F-FDG in diagnosing cervical cancer pelvic lymph node.4.There was no statistical significance between ^99mTc-Galacto-RGD₂ and 18F-FDG imaging in 34 cases of cervical cancer patients with preoperative staging??2=2.800,P=0.247,P>0.05?.that is,^99mTc-Galacto-RGD₂ imaging had a similar efficiency with 18F-FDG in accurate staging of cervical cancer.they were consistent in 28 patients with cervical cancer,and were not consistent with the staging of cervical cancer in 6 patients.Conclusion:1.^99mTc-Galacto-RGD₂ is evidently gathered in the tissue of cervical cancer and the contrast ratio between the lesion and the surrounding soft tissue is well,with a clear image quality.2.^99mTc-Galacto-RGD₂ has a similar efficiency in diagnosing primary lesion of cervical cancer,detecting pelvic lymph node metastasis and accurate preoperative clinical staging.3.^99mTc-Galacto-RGD₂ is a promising tumor receptor imaging agent.Part III The expression and clinical significance of integrin?v?3 incervical carcinomaObjectives: By detecting the expression condition of integrin?v?3 in the tissue of cervical cancer using immunohistochemistry test,it is to discuss the relevance between radioactive uptake of ^99mTc-Galacto-RGD₂ and integrin?v?3 in the cervical cancer tissue and the relevance between radioactive uptake of ^99mTc-Galacto-RGD₂,expression of integrin?v?3 in the cervical cancer tissue and the differentiated degree of cervical cancer.Method: The research objects are the same with that in the first part.The biopsy or postoperative pathological tissue of 40 patients with suspected cervical cancer was collected.The immunohistochemistry test was adopted in this study to detect the expression condition of integrin?v?3,SPSS19.0 statistical software for data processing.Variance analysis or independent sample t-test,non-parametric rank sum test,chi-square test or Fisher exact test and Spearman rank correlation coefficient were adopted in this study.P values less than 0.05 were considered to be statistically significant.Result:1.Integrin?v?3 was negatively or very small expressed in cervical benign lesions;the positive staining of integrin?v?3 in the tissue of cervical cancer presented different degrees of staining,from brownness to sepia,mainly expressed in cytoplasm and cytomembrane of cancer cells.The karyon was not stained and there were some positive cells in the carcinoma stroma.Integrin?v?3 was diffusely distributed in the tissue of cervical cancer.2.T/M value of ^99mTc-Galacto-RGD₂ in cervical benign lesions and cervical cancer tissue were 3.32±0.46,6.04±1.52,respectively;there was statistical significance between them?t=8.464,P=0.000,P<0.05?.The uptake value of ^99mTc-Galacto-RGD₂ in the cervical cancer tissue was higher than that in cervical benign lesions.The positive rate of integrin?v?3 in cervical benign lesions and cervical cancer tissue were 16.7%?1/6?and 79.4%?27/34?,respectively and there was statistical significance??2=9.561,P=0.003,P<0.05?,that is,the expression of integrin?v?3 in the cervical cancer tissue was higher than that in the cervical benign lesions.3.TM value of ^99mTc-Galacto-RGD₂ of cervical cancer patients from the high,middle and low differentiation group were 4.55±0.80,6.32±1.17,7.71±0.86,respectively and the relevant medians were 4.69?3.73,5.21?,6.58?5.28,7.36?,7.54?7.49,7.75?.T/M value of three different differentiation degrees had statistical significance??2=19.259,P=0.000,P<0.05?,that is,the ratios of radioactive uptake value/muscle of cervical cancer patients from the high,middle and low differentiation group had difference.Pairwise comparison indicated that T/M of ^99mTc-Galacto-RGD₂ between the high,middle and low differentiation had difference: low differentiation>middle differentiation>high differentiation.The relevance between uptake of ^99mTc-Galacto-RGD₂ in the cervical cancer and the differentiation degree was rs=-0.764,suggesting that the uptake value of ^99mTc-Galacto-RGD₂ in the tissue of cervical cancer is negatively related to the differentiated degree of cervical cancer tissue,that is,the lower the differentiation degree is,the higher the uptake of ^99mTc-Galacto-RGD₂ will be.4.The expression of integrin?v?3 in cervical carcinoma differtiation group??2=10.936,P=0.004,P<0.05?,The relevance between expression of integrin?v?3 and the differentiation degree of cervical cancer was rs=-0.495,suggesting that the expression of integrin?v?3 is negatively related to the differentiated degree of cervical cancer tissue.In pairwise comparison,the positive expression degree of integrin?v?3 in the low differentiation group was higher than that of the high differentiation group and the middle differentiation group.There was no statistical significance in the positive degree of integrin?v?3 expression between the high differentiation group and the middle differentiation group.5.There was statistical significance between the expression of integrin?v?3 and TM value of ^99mTc-Galacto-RGD₂??2=2.800,P=0.247,P>0.05?.that is,the relevance between expression of integrin?v?3 and the TM value of ^99mTc-Galacto-RGD₂ was rs=-0.495,suggesting that the expression of integrin?v?3 is positively related to the TM value of ^99mTc-Galacto-RGD₂.Conclusion:1.Integrin?v?3 is positively expressed in cervical cancer,Integrin?v?3 was negatively or very small expressed in cervical benign lesions.2.The expression of integrin?v?3 and the radioactive uptake value of ^99mTc-Galacto-RGD₂ in the tissue of cervical cancer are higher than that in benign cervical lesions.3.The expression of integrin?v?3 and the local radioactive uptake value of ^99mTc-Galacto-RGD₂ in the tissue of cervical cancer are negatively related to the differentiated degree of cervical cancer tissue.the expression of integrin?v?3 is negatively related to the TM value of ^99mTc-Galacto-RGD₂.4.The positive degree of integrin?v?3 in the low-differentiated tissue is higher than that of the high-differentiated and the middle-differentiated;the high-differentiated and the middle-differentiated cervical cancer has no difference in the expression of integrin?v?3.