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The Clinical Application Of99mTc-HYNIC-PSMA Small Molecule Inhibitor SPECT/CT In Diagnosis Of Prostate Cancer

Posted on:2021-05-05Degree:MasterType:Thesis
Country:ChinaCandidate:X M RuanFull Text:PDF
GTID:2404330602973856Subject:Imaging and nuclear medicine
Abstract/Summary:PDF Full Text Request
Background and objective:Prostate cancer(PCa)is commonly found in the Prostate epithelium,and its pathological types include adenocarcinoma,ductal adenocarcinoma,squamous cell carcinoma and adenosquamous cell carcinoma,of which adenocarcinoma accounts for over 95%.According to the data from cancer centers in China,the incidence of PCa in the urinary system has been the highest since 2008,with an annual increase of more than 5%.Therefore,early accurate diagnosis of PCa has become a research hotspot.Serum prostate-specific antigen(PSA)is a common indicator for early clinical screening of PCa,but when PSA level tends to the diagnostic gray scale(TPSA at 4-10 ng/ml),the diagnostic sensitivity and specificity will be reduced,and prostatic hyperplasia and inflammation can also lead to PSA elevation.Therefore,PSA detection alone cannot accurately determine Prostate diseases.In recent years,the multi-mode imaging technology has made great progress in PCa diagnosis and research.Transrectal ultrasound can clearly display the morphological structure and blood flow of the prostate,with high cost performance and availability.Enhanced CT can show the anatomical structure of the prostate and its relationship with surrounding tissues,but MR]is more advantageous in showing the soft tissue and the structural division of the prostate.18F-FDG PET/CT can be used for PCa staging and comprehensive evaluation,but FDG uptake in some lesions is low and false negative rate is high.Prostate specific membrane antigen(prostate specific be antigen,PSMA)secreted by the surrounding the epithelial cells at the top of the prostatic ducts,for most of the PCa cells of type II transmembrane protein expression,especially in the low differentiation,metastatic and androgen dependent PCa cell surface,expressing quantity can reach 100-1000 times the normal tissue,in normal tissues,kidney,intestines,etc.)expression level is very low.PSMA is phagocytized by cells after binding to ligands such as specific antibodies and small molecule antagonists,and PSMA will be retained in lysosomes or released into the cytoplasm.Based on this biological effect,PSMA is highly specific as a diagnostic target of PCa.Studies have confirmed that in low level PSA cases,the "Ga-PSMA-HBED-CC small-molecule inhibitor probe has higher diagnostic accuracy of PCa than the standard 18f-fluoromethylcholine PET/CT,but it is difficult to be popularized due to the limitation of equipment and positron imaging agent.SPECT and 99mTc labeled imaging agent can be popularized.Previous studies have shown that 99mtc-hynic-psma imaging diagnosis of PCa has a high sensitivity(70-90%)and specificity(more than 85%),and the detection rate of lesions is positively correlated with PSA level,but for cases with PSA gray scale,the diagnosis sensitivity is low.It has been reported that prostate-specific antigen density(prostate-specific antigen density,PSAD(the ratio of PSA to prostate volume)is of higher diagnostic value than PSA and can effectively avoid the influence of PSA gray area,but there has been no report on the combined diagnosis of PSMA imaging and PSAD.In this study,the diagnostic titer of 99mTc-HYNIC-PSMA SPECT/CT imaging and PSAD,as well as the gain value of the combination of the two,were discussed,so as to give full play to the diagnostic advantages of this technique in the accurate diagnosis and treatment of PCa.Methods:The subjects of this study were 31 patients with highly suspected prostate cancer in henan provincial people's hospital.All the patients did not receive chemoradiotherapy,endocrine therapy or/or castration therapy before PSMA SPECT/CT examination.PSAD=TPSA/prostate volume(V)was calculated after serum PSA(TPSA)and FPSA were measured in all 4 cases.Prostate volume and PSAD were not obtained due to severe invasion of surrounding tissues.All patients received PSMA SPECT/CT examination,intravenous injection of 99mtc-hynic-psma 15-25 mCi,and 2 h after the injection,whole-body plane+local computed tomography/CT imaging,the acquisition device was GE Discovery NM/CT type 670 SPECT/CT,and the image was post-processed and the area of interest was labeled.PSMA positive focus judgment criteria:visual analysis mainly,nuclear medicine whole body Tomography showed increased radioactivity in tissues with normal or abnormal local morphology and excluded physiological uptake or distribution(salivary gland,orbit,liver,gallbladder,spleen,small intestine,kidney and bladder)as a lesion.If local histomorphology was abnormal,but no abnormal radioabsorption was found in the corresponding site,the lesion was regarded as PSMA negative or considered as a non-prostate cancer source.The consistency of 99mTc-HYNIC-PSMA SPECT/CT imaging results and pathological results were analyzed by spearman grade analysis;the sensitivity,specificity,accuracy,positive predictive value and negative predictive value of 99mTcHYNIC-PSMA SPECT/CT imaging were calculated.The difference of TPSA,FPSA,F/TPSA and PSAD between benign group and malignant group was compared by Mann-Whitney U rank sum test.When P<0.05,the difference was statistically significant,and making a meaningful impact factor.Using Medcalc software to analyze the the influential factors by ROC curves,the significant influencing factors are obtained.Pearson linear correlation was used to analyze the relationship between 99mTc-HYNIC-PSMA SPECT/CT imaging and significant influential factors in the diagnosis of prostate cancer,and the sensitivity,specificity and accuracy were calculated.Result1.Distribution in vivo after 2 hours of intravenous injection of 99mTc-HYNIC-PSMA small molecule inhibitor:physiological distribution of salivary glands,lacrimal glands,liver,gallbladder,spleen,small intestine,kidney and bladder,with the highest radioactive distribution of bladder and kidney.Next is salivary gland,lacrimal gland;Then liver,gallbladder,spleen,intestine,cardiopulmonary tissue;The latter is bone and muscle;The brain has the lowest distribution of radioactivity.No adverse reactions were found in all patients during follow-up.2.Consistency analysis of PSMA SPECT/CT and pathology.In the malignant group,20 patients(2 patients with false negative and 1 patient with false positive)had positive PSMA SPECT/CT.The imaging and pathological consistency was rs=0.78(P=0.00).The diagnostic sensitivity was 90.91%(20/22),specificity 88.89%(8/9),accuracy 90.32%(28/31),positive predictive value 95.24%(20/21)and negative predictive value 80.00%(8/10).3.Correlation analysis of TPSA,FPSA,F/TPSA and PS AD with prostate cancer diagnosis.In the malignant group(22 cases),the levels of PSA were:FPSA 7.27(1.85,122.75),TPSA 52.55(14.99,1124.00),F/TPSA 0.12(0.09,0.16),PSAD(n=18)1.23(0.55,25.59);in the benign group(9 cases),the levels of PSA were:FPSA 1.72(0.90,2.29),TPSA 11.13(6.21,18.85),F/TPSA 0.12(0.10,0.19),PSAD 0.12(0.08,0.19);comparing the two groups of data,we found that FPSA,TPSA and PSAD(Z=2.70,P=0.01;Z=2.8 7,P=0.00;Z=3.91,P=0.00)were statistically significant;the difference in F/TPSA(Z=0.37;P=0.71)was not statistically significant The analysis of ROC curve shows that PSAD has the most diagnostic value,and its AUC is 0.97(FPSA and TPSA are 0.86),and when PSAD>0.36,the sensitivity of the diagnosis of prostate cancer was 88.9%,the specificity was 100%,and the Youden index was 0.89.4.Results of 99mTc-HYNIC-PSMA SPECT/CT imaging were correlated with PSAD level.Among the PSAD values of 27 patients,18 were pathologically diagnosed as malignant and 9 as benign,In the 99mTc-HYNIC-PSMA SPECT/CT imaging group,the lowest PSAD level was 0.12,and in the negative group,the highest PSAD level was 0.36.In all patients with PSAD<0.10,99mtc-hynic-psma SPECT/CT imaging found no prostate cancer foci,as did MRI.Therefore,when PSAD>0.10 was used as the critical value,the sensitivity of 99mTc-HYNIC-PSMA SPECT/CT imaging to detect prostate cancer was 94.44%(17/18),the specificity was 85.71%(6/7),the accuracy was 92.00%(23/25),and the correlation coefficient r=0.80.When PSAD>0.15 was used as the critical value,the sensitivity of 99mTc-HYNIC-PSMA SPECT/CT imaging to prostate cancer detection was 94.18%(16/17),the specificity was 100%(4/4),and the accuracy was 95.24%(20/21),the correlation coefficient r=0.86.When PSAD>0.20 was used as the critical value,the sensitivity of 99mTc-HYNIC-PSMA SPECT/CT imaging to prostate cancer detection was 94.18%(16/17),the specificity was 100%(2/2),the accuracy was 94.74%(1 8/19),and the correlation coefficient r=0.79.Conclusion(1)99mTc-HYNIC-PSMA small molecule inhibitor imaging agent distribution in the body has a high degree of stability and specificity,and urinary system excretion as the main route,secondary route is liver,intestine,can be quickly removed by non-target tissues,is a safe and reliable way of examination.(2)99mTc-HYNIC-PSMA SPECT/CT imaging has a high value in the diagnosis of PCa,with a high degree of consistency with the pathological results.The consistency is(rs=0.78,p=0.00),the diagnostic sensitivity is 90.91%,the specificity is 88.89%,the accuracy is 90.32%,the positive predictive value is 95.24%and the negative predictive value is 80.00%.(3)The levels of the tumor marker PSA and its derived indexes(F/TPSA and PSAD)are closely related to PCa,among which PSAD has the highest diagnostic value(AUC=0.97),and when PSAD>is 0.36,the diagnostic sensitivity of PCa is 88.9%,the specificity is 100%,and the yodan index is 0.89.(4)The diagnosis of PCa with 99mTc-HYNIC-PSMA SPECT/CT imaging was positively correlated with PSAD,and PSAD?0.15 was the optimal threshold for the diagnosis of PCa with 99mtc-hynic-psma SPECT/CT.
Keywords/Search Tags:Prostate cancer, PSMA, SPECT/CT imaging, PSA, PSAD
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