Background We previously reported that iodine-131（131^I）-Iabeled anti-pro-gastrin-releasing peptide （ProGRP（31-98）） monoclonal antibody D-D3 could selectively accumulate in the tumor sites of nude mice bearing s...Background We previously reported that iodine-131（131^I）-Iabeled anti-pro-gastrin-releasing peptide （ProGRP（31-98）） monoclonal antibody D-D3 could selectively accumulate in the tumor sites of nude mice bearing small cell lung cancer （SCLC） xenografts. However, 1311-D-D3 was cleared slowly from the body, and the best radioimmunoimaging time for SCLC was 72-96 hours after injection. The aims of this study were to radiolabel anti-ProGRP（31-98） D-D3 monoclonal antibody with technetium-99m（99m^Tc） and to investigate the biodistribution of this antibody in healthy ICR mice. Methods D-D3was labeled with 99m^Tc via the 2-mercaptoethanol reduction method. 99m^Tc-D-g3 was purified by the gel column separation method. The labeling efficiency and radiochemical purity were measured by thin-layer chromatography. The immunological activity of 99m^Tc-D-O3 was determined with cell conjugation assays. 99m^Tc-D-D3 was injected into healthy ICR mice via a tail vein, and all the healthy ICR mice were sacrificed by cervical dislocation at a designated time. Then, the blood and major organs were removed and weighed, and counted in a gamma scintillation counter to determine the percentage of the injected dose per gram （%ID/g）. Results The labeling rate and the radiochemical purity of 99m^TC-D-D3 were （73.87±2.89）% and （94.13±4.49）%, respectively. The immunobinding rates of 99m^Tc-O-D3 to the human small cell lung cancer NCI-H446 cell line and lung adenocarcinoma A549 cell line were （81.2±2.37）% and （24.3±1.46）%, respectively. The distribution data of normal ICR mice demonstrated that 99m^TC-D-D3was mainly distributed in the liver, kidney and lung, and less in the brain tissue and muscle. Conclusions 99m^Tc-D-D3 antibody not only had high radiochemical purity, but also had good stability both in vitro and in vivo, and maintained good immunological activity. 99m^Tc-D-D3 was metabolized mainly in the kidney and liver, and the blood radioactivity decreased rapidly. Thus, 99m^Tc-O-D3 is conducive to the radioimmunoimaging of SCLC.展开更多
Background Monoclonal antibodies （mAbs） such as DD3,raised against progastrin-releasing peptide（31-98） （ProGRP（31-98）） antigen,have been used to target small cell lung cancer （SCLC）.However,as an intact mAb,...Background Monoclonal antibodies （mAbs） such as DD3,raised against progastrin-releasing peptide（31-98） （ProGRP（31-98）） antigen,have been used to target small cell lung cancer （SCLC）.However,as an intact mAb,DD3 is cleared slowly from the body,with an optimal radioimmunoimaging time of 72 hours.More recently,a singlechain antibody fragment has demonstrated reduced excretion time in blood and normal tissues and is increasingly used in diagnostic cancer research.Thereby,it potentially increases the radioimmunoimaging efficacy.However,there have been few studies with this antibody fragment.The aim of this study was to characterize the preliminary radioimmunoimaging and biodistribution of 1311I-anti-ProGRP（31-98）scFv in nude mice bearing SCLC xenografts.Methods Anti-ProGRP（31-98） scFv was used to detect ProGRP expression by flow cytometry analysis and immunohistochemistry.131I-anti-ProGRP（31-98） scFv was injected intravenously into healthy Kunming mice and the percentage injected dose per gram （%ID/g） in various organs was calculated.Similarly,the %ID/g and tumor/non-tumor ratio in xenograft-bearing mice was calculated.After injection of 131I-anti-ProGRP（31-98） scFv,treated mice were imaged at 1,24,and 30 hours.Then the tumor/base ratios were calculated.Results ProGRP was highly expressed in NCI-H446 cells and xenograft tissue.The metabolism of 131I-anti-ProGRP（31-98） scFv in healthy mice was consistent with a first-order and two-compartment model; T1/2α and T1/2β were 10.2 minutes and 5 hours 18 minutes,respectively.The %ID/g of 131I-anti-ProGRP（31-98） scFv in xenografts was much higher than in healthy tissues at 12 hours after injection,reaching a maximum of （5.38±0.92） %ID/g at 24 hours.Successful imaging of xenograft tissue was achieved as early as 1 hour post-injection and persisted until 30 hours,with 24 hours proving optimal.Conclusion 131I-anti-ProGRP（31-98）scFv shows highly selective tumor uptake with low accumulation in normal tissues and rapid blood clearance,indicating thatit could be a promising agent for SCLC radioimmunoimaging.展开更多
Background Lung cancer is one of the most common malignancies in the world and one of the leading cancers that result in death. The aim of this study was to evaluate and compare the diagnostic value of the serum tumor...Background Lung cancer is one of the most common malignancies in the world and one of the leading cancers that result in death. The aim of this study was to evaluate and compare the diagnostic value of the serum tumor marker pro-gastrin-releasing peptide 31-98 （ProGRP31-98） to pathological diagnosis as reference standard in patients with suspected small cell lung cancer （SCLC）.Methods Literature searches covering 1978 through to 2009 were performed in Pubmed, OVID, MEDLINE, EMbase,Cancerlit, China National Knowledge Infrastructure （CNKI）, and CBM using the key search words; ＇small cell lung cancer＇,＇tumor marker＇, ＇ProGRP31-98＇ and ＇diagnostic tests＇, ＇ELISA＇, ＇EIA＇ and ＇diagnostic accuracy＇. Studies were collected and data analyzed to evaluate the diagnostic value of serum ProGRP31-98 levels for the diagnosis of SCLC compared with pathology. Eligibility criteria for inclusion in the analysis were based on criteria for diagnostic research published by the Cochrane Screening and Diagnostic Tests Methods Group （SDTMG）. The characteristics of the included articles were appraised and the data were extracted from the original articles for further statistical analysis of study heterogeneity using Review Manager 4.2 software. Based on study heterogeneity analysis, a suitable ＇effect＇ model was selected to calculate pooled sensitivity and specificity by meta-analysis. A Summary Receiver Operating Characteristic （SROC） curve and the area under the curve （AUC） were generated and sensitivity analysis conducted.Results A total of 22 articles were entered into this meta-review, including 11 English articles with a quality at level C. In total, the studies involved 6759 subjects, of which 1470 were diagnosed with SCLC by pathology, and 5289 subjects diagnosed with non-SCLC （NSCLC）. The meta-analysis showed that heterogeneity among studies was high （P=0.00001,（I2）=86.8%）. With ELISA, the pooled sensitivity was 0.72 （0.70 to 0.75 at 95% Cl） and the pooled specificity was 0.93 （0.92to 0.94 at 95% Cl）; the SROC and the AUC were 0.8817. These data suggest that ProGRP31-98 has a relatively high rate of missed diagnosis （28%）, but a relatively low rate of misdiagnosis （7%）.Conclusion From meta-analysis, we concluded that serum ProGRP31-98 is a valuable marker with a high specificity for diagnosis of SCLC with a similar diagnostic accuracy to pathology.展开更多
文摘Background We previously reported that iodine-131（131^I）-Iabeled anti-pro-gastrin-releasing peptide （ProGRP（31-98）） monoclonal antibody D-D3 could selectively accumulate in the tumor sites of nude mice bearing small cell lung cancer （SCLC） xenografts. However, 1311-D-D3 was cleared slowly from the body, and the best radioimmunoimaging time for SCLC was 72-96 hours after injection. The aims of this study were to radiolabel anti-ProGRP（31-98） D-D3 monoclonal antibody with technetium-99m（99m^Tc） and to investigate the biodistribution of this antibody in healthy ICR mice. Methods D-D3was labeled with 99m^Tc via the 2-mercaptoethanol reduction method. 99m^Tc-D-g3 was purified by the gel column separation method. The labeling efficiency and radiochemical purity were measured by thin-layer chromatography. The immunological activity of 99m^Tc-D-O3 was determined with cell conjugation assays. 99m^Tc-D-D3 was injected into healthy ICR mice via a tail vein, and all the healthy ICR mice were sacrificed by cervical dislocation at a designated time. Then, the blood and major organs were removed and weighed, and counted in a gamma scintillation counter to determine the percentage of the injected dose per gram （%ID/g）. Results The labeling rate and the radiochemical purity of 99m^TC-D-D3 were （73.87±2.89）% and （94.13±4.49）%, respectively. The immunobinding rates of 99m^Tc-O-D3 to the human small cell lung cancer NCI-H446 cell line and lung adenocarcinoma A549 cell line were （81.2±2.37）% and （24.3±1.46）%, respectively. The distribution data of normal ICR mice demonstrated that 99m^TC-D-D3was mainly distributed in the liver, kidney and lung, and less in the brain tissue and muscle. Conclusions 99m^Tc-D-D3 antibody not only had high radiochemical purity, but also had good stability both in vitro and in vivo, and maintained good immunological activity. 99m^Tc-D-D3 was metabolized mainly in the kidney and liver, and the blood radioactivity decreased rapidly. Thus, 99m^Tc-O-D3 is conducive to the radioimmunoimaging of SCLC.
文摘Background Monoclonal antibodies （mAbs） such as DD3,raised against progastrin-releasing peptide（31-98） （ProGRP（31-98）） antigen,have been used to target small cell lung cancer （SCLC）.However,as an intact mAb,DD3 is cleared slowly from the body,with an optimal radioimmunoimaging time of 72 hours.More recently,a singlechain antibody fragment has demonstrated reduced excretion time in blood and normal tissues and is increasingly used in diagnostic cancer research.Thereby,it potentially increases the radioimmunoimaging efficacy.However,there have been few studies with this antibody fragment.The aim of this study was to characterize the preliminary radioimmunoimaging and biodistribution of 1311I-anti-ProGRP（31-98）scFv in nude mice bearing SCLC xenografts.Methods Anti-ProGRP（31-98） scFv was used to detect ProGRP expression by flow cytometry analysis and immunohistochemistry.131I-anti-ProGRP（31-98） scFv was injected intravenously into healthy Kunming mice and the percentage injected dose per gram （%ID/g） in various organs was calculated.Similarly,the %ID/g and tumor/non-tumor ratio in xenograft-bearing mice was calculated.After injection of 131I-anti-ProGRP（31-98） scFv,treated mice were imaged at 1,24,and 30 hours.Then the tumor/base ratios were calculated.Results ProGRP was highly expressed in NCI-H446 cells and xenograft tissue.The metabolism of 131I-anti-ProGRP（31-98） scFv in healthy mice was consistent with a first-order and two-compartment model; T1/2α and T1/2β were 10.2 minutes and 5 hours 18 minutes,respectively.The %ID/g of 131I-anti-ProGRP（31-98） scFv in xenografts was much higher than in healthy tissues at 12 hours after injection,reaching a maximum of （5.38±0.92） %ID/g at 24 hours.Successful imaging of xenograft tissue was achieved as early as 1 hour post-injection and persisted until 30 hours,with 24 hours proving optimal.Conclusion 131I-anti-ProGRP（31-98）scFv shows highly selective tumor uptake with low accumulation in normal tissues and rapid blood clearance,indicating thatit could be a promising agent for SCLC radioimmunoimaging.
文摘Background Lung cancer is one of the most common malignancies in the world and one of the leading cancers that result in death. The aim of this study was to evaluate and compare the diagnostic value of the serum tumor marker pro-gastrin-releasing peptide 31-98 （ProGRP31-98） to pathological diagnosis as reference standard in patients with suspected small cell lung cancer （SCLC）.Methods Literature searches covering 1978 through to 2009 were performed in Pubmed, OVID, MEDLINE, EMbase,Cancerlit, China National Knowledge Infrastructure （CNKI）, and CBM using the key search words; ＇small cell lung cancer＇,＇tumor marker＇, ＇ProGRP31-98＇ and ＇diagnostic tests＇, ＇ELISA＇, ＇EIA＇ and ＇diagnostic accuracy＇. Studies were collected and data analyzed to evaluate the diagnostic value of serum ProGRP31-98 levels for the diagnosis of SCLC compared with pathology. Eligibility criteria for inclusion in the analysis were based on criteria for diagnostic research published by the Cochrane Screening and Diagnostic Tests Methods Group （SDTMG）. The characteristics of the included articles were appraised and the data were extracted from the original articles for further statistical analysis of study heterogeneity using Review Manager 4.2 software. Based on study heterogeneity analysis, a suitable ＇effect＇ model was selected to calculate pooled sensitivity and specificity by meta-analysis. A Summary Receiver Operating Characteristic （SROC） curve and the area under the curve （AUC） were generated and sensitivity analysis conducted.Results A total of 22 articles were entered into this meta-review, including 11 English articles with a quality at level C. In total, the studies involved 6759 subjects, of which 1470 were diagnosed with SCLC by pathology, and 5289 subjects diagnosed with non-SCLC （NSCLC）. The meta-analysis showed that heterogeneity among studies was high （P=0.00001,（I2）=86.8%）. With ELISA, the pooled sensitivity was 0.72 （0.70 to 0.75 at 95% Cl） and the pooled specificity was 0.93 （0.92to 0.94 at 95% Cl）; the SROC and the AUC were 0.8817. These data suggest that ProGRP31-98 has a relatively high rate of missed diagnosis （28%）, but a relatively low rate of misdiagnosis （7%）.Conclusion From meta-analysis, we concluded that serum ProGRP31-98 is a valuable marker with a high specificity for diagnosis of SCLC with a similar diagnostic accuracy to pathology.
