Objective:To explore the potential of the novel fibroblast activation protein (FAP)-targeted theranostic agent 68Ga/ 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-2P (FAP inhibitor (FAPI)) 2 in microsatellite stable (MSS) colorectal cancer, and to evaluate the efficacy and underlying mechanism of 177Lu-DOTA-2P(FAPI) 2 in combination with immune checkpoint inhibitors (ICIs). Methods:This study was a randomized, parallel-group design. DOTA-2P(FAPI) 2 was labeled with 68Ga or 177Lu respectively. The binding performance of DOTA-2P(FAPI) 2 to FAP was validated through in vitro cell experiments. FAP-positive CT26-FAP tumor-bearing mouse model was constructed, and microPET imaging and biodistribution were performed. The in vivo antitumor efficacy was assessed for the 177Lu-DOTA-2P(FAPI) 2 monotherapy, α programmed death-ligand 1 (PD-L1) monotherapy, and the combination of 177Lu-DOTA-2P(FAPI) 2 with αPD-L1 therapy groups. Changes in the tumor microenvironment were analyzed using single-cell RNA sequencing to elucidate the mechanism of the combined treatment. Independent-sample t test was used to analyze data. Survival analysis was performed using the log-rank test. Results:The labeling yields of 68Ga/ 177Lu-DOTA-2P(FAPI) 2 were both >90%, with the radiochemical purities both >95%. In vitro cellular uptake and blocking assays showed that FAPI-46 significantly inhibited the binding of 68Ga-DOTA-2P(FAPI) 2 to FAP in CT26-FAP cells, with the cellular uptake values at 60min of (51.5±0.8)% and (1.0±0.3)%, respectively ( t=102.40, P<0.001). MicroPET imaging showed that the tumor uptake of 68Ga-DOTA-2P(FAPI) 2 remained stable even at 4 h post-injection, with a significantly higher uptake value compared to 68Ga-FAPI-46 ((7.3±1.6) vs (3.7±0.2) percentage activity of injection dose per gram of tissue (%ID/g); t=3.87, P=0.018). The biodistribution results indicated significant tumor uptake of 177Lu-DOTA-2P(FAPI) 2 even at 24 h post-injection ((4.30±0.52)%ID/g). The combination of 177Lu-DOTA-2P(FAPI) 2 and αPD-L1 achieved the 30-day survival rate of 100%, which was significantly superior to that of the control group (saline injection; χ2=9.53, P=0.002). Further mechanistic studies revealed that the combination therapy reprogramed the tumor microenvironment, enhanced anti-tumor intercellular communication, and activated signaling pathways such as Fas-FasL between T cells/natural killer (NK) cells and tumor cells, thereby synergistically inhibiting tumor progression. Conclusions:68Ga/ 177Lu-DOTA-2P(FAPI) 2 exhibits theranostic potential for MSS colorectal cancer. The combination of 177Lu-DOTA-2P(FAPI) 2 with ICIs may significantly prolong survival, demonstrating significant potential for clinical translation.

Objective:To explore the potential of the novel fibroblast activation protein (FAP)-targeted theranostic agent 68Ga/ 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-2P (FAP inhibitor (FAPI)) 2 in microsatellite stable (MSS) colorectal cancer, and to evaluate the efficacy and underlying mechanism of 177Lu-DOTA-2P(FAPI) 2 in combination with immune checkpoint inhibitors (ICIs). Methods:This study was a randomized, parallel-group design. DOTA-2P(FAPI) 2 was labeled with 68Ga or 177Lu respectively. The binding performance of DOTA-2P(FAPI) 2 to FAP was validated through in vitro cell experiments. FAP-positive CT26-FAP tumor-bearing mouse model was constructed, and microPET imaging and biodistribution were performed. The in vivo antitumor efficacy was assessed for the 177Lu-DOTA-2P(FAPI) 2 monotherapy, α programmed death-ligand 1 (PD-L1) monotherapy, and the combination of 177Lu-DOTA-2P(FAPI) 2 with αPD-L1 therapy groups. Changes in the tumor microenvironment were analyzed using single-cell RNA sequencing to elucidate the mechanism of the combined treatment. Independent-sample t test was used to analyze data. Survival analysis was performed using the log-rank test. Results:The labeling yields of 68Ga/ 177Lu-DOTA-2P(FAPI) 2 were both >90%, with the radiochemical purities both >95%. In vitro cellular uptake and blocking assays showed that FAPI-46 significantly inhibited the binding of 68Ga-DOTA-2P(FAPI) 2 to FAP in CT26-FAP cells, with the cellular uptake values at 60min of (51.5±0.8)% and (1.0±0.3)%, respectively ( t=102.40, P<0.001). MicroPET imaging showed that the tumor uptake of 68Ga-DOTA-2P(FAPI) 2 remained stable even at 4 h post-injection, with a significantly higher uptake value compared to 68Ga-FAPI-46 ((7.3±1.6) vs (3.7±0.2) percentage activity of injection dose per gram of tissue (%ID/g); t=3.87, P=0.018). The biodistribution results indicated significant tumor uptake of 177Lu-DOTA-2P(FAPI) 2 even at 24 h post-injection ((4.30±0.52)%ID/g). The combination of 177Lu-DOTA-2P(FAPI) 2 and αPD-L1 achieved the 30-day survival rate of 100%, which was significantly superior to that of the control group (saline injection; χ2=9.53, P=0.002). Further mechanistic studies revealed that the combination therapy reprogramed the tumor microenvironment, enhanced anti-tumor intercellular communication, and activated signaling pathways such as Fas-FasL between T cells/natural killer (NK) cells and tumor cells, thereby synergistically inhibiting tumor progression. Conclusions:68Ga/ 177Lu-DOTA-2P(FAPI) 2 exhibits theranostic potential for MSS colorectal cancer. The combination of 177Lu-DOTA-2P(FAPI) 2 with ICIs may significantly prolong survival, demonstrating significant potential for clinical translation.

Glioblastoma(GBM)is a widely occurring and highly invasive central nervous system tumor.Its occurrence and development are closely related to multiple molecular mechanisms,making treatment and prognosis challenging.Integrin α7(ITGA7)is a potential marker for glioblastoma stem cells,and its high expression is associated with poor prognosis in various solid tumor patients.In recent years,research on the pathogenesis of GBM involving ITGA7 has increased.This review summarizes recent studies on the role of ITGA7 in promoting GBM progression,including GBM cell biology,angiogenesis,signaling pathways,and the tumor microenvironment,with the aim of providing references for further understanding the mechanisms of GBM occurrence and development and the exploration of therapeutic targets.

Erythropoietic protoporphyria （EPP） is a rare inherited metabolic disease that often involves skin， blood， and nervous systems， and EPP with the main manifestations of severe liver damage and acute abdominal pain is extremely rare. By reviewing the clinical data and genetic testing results of a patient with EPP， this article discusses the clinical features and pathogenic genes of this disease， in order to improve the understanding of the disease among hepatologists and achieve early diagnosis and treatment.

Glioblastoma(GBM)is a widely occurring and highly invasive central nervous system tumor.Its occurrence and development are closely related to multiple molecular mechanisms,making treatment and prognosis challenging.Integrin α7(ITGA7)is a potential marker for glioblastoma stem cells,and its high expression is associated with poor prognosis in various solid tumor patients.In recent years,research on the pathogenesis of GBM involving ITGA7 has increased.This review summarizes recent studies on the role of ITGA7 in promoting GBM progression,including GBM cell biology,angiogenesis,signaling pathways,and the tumor microenvironment,with the aim of providing references for further understanding the mechanisms of GBM occurrence and development and the exploration of therapeutic targets.

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.
Humans ; China/epidemiology* ; Cross Infection/epidemiology* ; Intensive Care Units/statistics & numerical data* ; Quality Control ; Quality Indicators, Health Care/statistics & numerical data* ; Sepsis/therapy* ; East Asian People/statistics & numerical data*

Objective To investigate the risk factors of perioperative complications of laparoscopic radical distal gastrectomy and influence of body shape on the short-term therapeutic effects.Methods The retrospective case-control study was conducted.The clinicopathological data of 506 patients (328 males and 178 females,average age 60 years with the range of 24-85 years) who underwent laparoscopic radical distal gastrectomy+D2 lymph nodes dissection in the 8 clinical centers between March 2016 and November 2018 were collected,including 143 in the First Affiliated Hospital of Xiamen University,66 in the Affiliated Hospital of Qinghai University,66 in the Second Affiliated Hospital of Wenzhou Medical University,64 in the Zhongshan Hospital of Xiamen University,54 in the Affiliated Hangzhou First people's Hospital of Zhejiang University School of Medicine,48 in the Zhangzhou Affiliated Hospital of Fujian Medical University,35 in the Affiliated Quanzhou First Hospital of Fujian Medical University,30 in the Second Affiliated Hospital of Xiamen Medical College.The maximum thickness of subcutaneous fat at the level of umbilicus (USCF),the maximum vertical distance between the anterior abdominal skin and the back skin at the level of the umbilicus (UAPD),the maximum horizontal distance between the anterior abdominal skin and the back skin at the level of the umbilicus (UTD),the maximum verticaldistance between the anterior abdominal skin and the back skin at the level of the xiphoid bone (XAPD),the maximum horizontal distance between the.anterior abdominal skin and the back skin at the level of the xiphoid bone (XTD),the distance between the anterior abdominal skin and the root of celiac artery (CAD) and the maximum horizontal distance at a right angle to CAD (CATD) were measured using preoperative imaging examinations.Observation indicators:(1) intraoperative and postoperative situations;(2) follow-up situations;(3) risk factors analysis of perioperative complications;(4) influence of body shape related indexes on intraoperative situations and postoperative recovery:① Pearson univariate correlation analysis,② liner regression model analysis.Followup using outpatient examination and telephone interview was performed to detect the postoperative survival and tumor recurrence or metastasis up to December 2018.Measurement data with normal distribution were represented as Mean±SD.Measurement data with skewed distribution were described as M (range).Comparisons of count data were analyzed using the chi-square test.Comparisons of ordinal data were analyzed by Mann-Whitney U nonparametric test.Risk factors of perioperative complications of laparoscopic distal gastrectomy were analyzed by Logistic regression model.Influence of body shape related indexes on intraoperative situations and postoperative recovery was analyzed by Pearson univariate correlation analysis and liner regression model.Results (1) Intraoperative and postoperative situations:all the 506 patients underwent successful laparoscopic distal gastrectomy,including 103 with Billroth Ⅰ anastomosis,140 with Billroth Ⅱ anastomosis,201 with Billroth Ⅱ + Braun anastomosis,62 with Roux-en-Y anastomosis.The operation time,volume of intraoperative blood loss,number of lymph nodes dissected,time to postoperative anal exsufflation,time for initial fluid diet intake,time for initial semi-fluid diet intake and duration of postoperative hospital stay were (233±44)minutes,(102±86)mL,34±13,(3.6±1.5)days,(5.8±3.3)days,(8.3±3.8)days,(12.2±5.7)days respectively in the 506 patients.Of 506 patients,196 were defined as pathological stage Ⅰ,122 were defined as pathological stage Ⅱ and 188 were defined as pathological stage Ⅲ postoperatively.Of 506 patients,93 had 106 times of perioperative complications,including 33 times of pulmonary and upper respiratory infection,12 times of incisional infection,11 times of anastomotic leakage,11 times of abdominal infection,8 times of intestinal obstruction,8 times of gastroplegia,6 times of abdominal hemorrhage,5 times of bacteremia,3 times of anastomotic hemorrhage,3 times of lymph fluid leakage,2 times of pancreatic leakage,1 time of urinary infection,1 time of anatomotic stenosis,1 time of deep venous thrombosis and 1 time of pulmonary embolism;the same patient can merge multiple complications.Eleven patients were in the Clavien-Dindo classification ≥ Ⅲ.(2) Follow-up situations:465 of 506 patients were followed up for 1-32 months with a median time of 12 months.During the follow-up,451 had postoperative survival and 38 had tumor recurrence or metastasis.(3) Risk factors analysis of perioperative complications.① Results of univariate analysis showed that age,body mass index (BMI),preoperative hemoglobin,preoperative serum albumin and XAPD were related factors affecting perioperative complications of laparoscopic distal gastrectomy (x2 =10.289,7.427,5.269,5.481,4.285,P＜ 0.05).② Results of multivariate analysis showed that age,BMI,preoperative serum albumin were independent related factors affecting perioperative complications of laparoscopic distal gastrectomy (odds ratio =1.033,1.118,0.937,95％ interval confidence:1.011-1.057,1.025-1.219,0.887-0.990,P＜0.05).(4) Influence of body shape related indexes on intraoperative situations and postoperative recovery.① Results of Pearson univariate correlation analysis showed correlations between UAPD,XAPD,CAD,CATD and volume of intraoperative blood loss (r=0.107,0.169,0.179,0.106,P＜0.05),between UAPD,XAPD,CAD and the number of lymph nodes dissected (r=-0.137,-0.143,-0.173,P＜0.05),between USCF,XAPD and time to postoperative anal exsufflation (r =0.122,0.109,P＜0.05),between USCF,XAPD,CAD and time for initial fluid diet intake (r=0.132,0.108,0.132,P＜0.05),between USCF,XAPD and duration of postoperative hospital stay (r=0.116,0.100,P＜0.05).② Results of liner regression model analysis showed a positive correlation between CAD and volume of intraoperative blood loss (r =6.776),a negative correlation between CAD and the number of lymph nodes dissected (r =-0.841),with statistically significant differences (t =2.410,-1.992,P＜ 0.05);a positive correlation between USCF and time to postoperative anal exsufflation (r=0.170),between USCF and time for initial fluid diet intake (r=0.365),between USCF and duration of postoperative hospital stay (r=0.636) respectively,with statisticallysignificant differences (t =2.188,1.981,2.107,P＜ 0.05).Conclusions Abdominal shape can influence intraoperative situations and postoperative recovery of laparoscopic distal gastrectomy,but cannot increase risks ofperioperative complications.Age,BMI and preoperative serum albumin are independent related factors affecting perioperative complications of laparoscopic distal gastrectomy.

Objective To investigate the effect of Jiawei-Xiaoyao powder on the levels of somatotropin and vasoaetive intestinal peptide (VIP) in patients with non-erosive reflux disease (NERD).Methods Seventy patients with liver-stagnation and spleen-deficiency NERD who met the inclusion criteria were divided into two groups according to the random number table,35 in each group.The treatment group was orally administered with Jiawei-Xiaoyao powder,and the control group was given oral omeprazole enteric-coated tablets and domperidone.Both groups were treated for 8 weeks.Plasma somatotropin and VIP levels were measured by ELISA.Results After treatment,plasma somatotropin levels (210.96 ± 16.85 pg/ml vs.195.75 ± 12.62 pg/ml,t=4.274) in the treatment group were significantly higher than that in the control group (P＜0.01),and plasma VIP level (16.12 ± 1.41 pg/ml vs.18.57 ± 2.68 pg/ml,t=4.786) in the treatment group was significantly lower than that in the control group (P＜0.01).Conclusions The Jiawei-Xiaoyao powder could reduce plasma VIP level in NERD patients,increase plasma somatotropin levels of NERD.

Objective To investigate the short-term clinical effects of selecting duodenal transection timing on laparoscopic-assisted distal gastrectomy (LADG).Methods The retrospective cohort study was conducted.The clinicopathological data of 239 gastric cancer (GC) patients undergoing LADG in the 5 medical centers between March 2016 and March 2018 were collected,including 104 in the First Affiliated Hospital of Xiamen University,45 in Zhangzhou Affiliated Hospital of Fujian Medical University,35 in Quanzhou Affiliated Hospital of Fujian Medical University,30 in the Second Affiliated Hospital of Xiamen Medical College,25 in Zhongshan Hospital of Xiamen University.Of 239 patients undergoing LADG + D2 lymph node dissection,107 receiving duodenal transection and then lymph node dissection in the upper region of pancreas after lymph node dissection in the lower region of pylorus and 132 receiving lymph node dissection in the upper region of pancreas and then duodenal transection were respectively divided into anterior approach group and posterior approach group.Sixty-four,8,16,14 and 5 patients in the anterior approach group and 40,37,19,16 and 20 patients in the posterior group respectively came from the First Affiliated Hospital of Xiamen University,Zhangzhou Affiliated Hospital of Fujian Medical University,Quanzhou Affiliated Hospital of Fujian Medical University,Second Affiliated Hospital of Xiamen Medical College and Zhongshan Hospital of Xiamen University.Observation indicators:(1) surgical and postoperative situations;(2) postoperative complications;(3) stratified analyses of surgical and postoperative situations in patients with different TNM staging,body mass index (BMI) and maximum tumor dimension;(4) follow-up and survival.Follow-up using outpatient examination and telephone interview was performed to detect postoperative overall survival and tumor recurrence or metastasis up to April 2018.Measurement data with normal distribution were represented as (-x)±s,and comparison between groups was analyzed using the independent-samples t test.Measurement data with skewed distribution were described as M (Q),and comparison between groups was analyzed using the nonparametric test.Comparisons of count data were analyzed using chi-square test or Fisher exact probability.Comparison of ordinal data was done by the rank-sum test.Results (1) Surgical and postoperative situations:all the patients underwent successful operation,without perioperative death.Number of lymph node dissection in the upper region of pylorus in the anterior and posterior approach groups were respectively 3.9±2.6 and 3.0±2.5,with a statistically significant difference between groups (t=2.778,P＜0.05).Cases with Billroth Ⅰ,Billroth Ⅱ,Billroth Ⅱ +Bruan and Roux-en-Y of digestive tract reconstruction,operation time,dissected times of lymph nodes in greater curvature of stomach,lower region of pylorus,upper region of pancreas and lesser curvature of stomach,cases with visible port vein,volume of intraoperative blood loss,number of overall lymph node dissection,numbers of lymph node dissection in greater curvature of stomach,lower region of pylorus,upper region of pancreas and lesser curvature of stomach,time to postoperative anal exsufflation,time for postoperative fluid diet intake,time for postoperative semi-fluid diet intake,intraperitoneal drainage-tube removal time and duration of postoperative hospital stay were respectively 16,32,47,12,(233.0±41.0)minutes,(14.6±5.4)tninutes,(21.9±6.3)nminutes,(32.7±6.8) minutes,(7.4±2.9)minutes,74,(87±73)mL,35.0±10.0,8.5±4.1,4.8±4.2,13.3±5.2,4.3± 3.3,(4.1±2.6)days,(5.4±2.8) days,(7.9± 3.5) days,(8.9± 2.9) days,(11.7± 4.5) days in the anterior approach group and 17,47,61,7,(243.0±44.0) minutes,(15.7±5.2) minutes,(23.1±8.0) minutes,(34.2±7.1) minutes,(7.9±2.8)minutes,79,(93±57)mL,33.0±10.0,8.1±4.8,5.3±4.9,12.5±5.6,3.8±2.4,(3.8±3.3)days,(5.0±3.6)days,(7.5±4.0) days,(8.5±3.8)days,(11.3±5.7) days in the posterior approach group,with no statistically significant difference between groups (x2 =3.431,t =-1.836,-1.546,-1.324,-1.634,-1.228,x2=2.552,t=-0.684,1.630,0.797,-0.871,1.148,1.314,0.954,0.951,0.884,1.065,0.694,P＞0.05).(2) Postoperative complications:cases with overall complications,anastomotic leakage,anastomotic stenosis,anastomotic bleeding,pancreatic fistula,postoperative gastroparesis,intra-abdominal hemorrhage,incision infection,pneumonia,intra-abdominal infection,bacteremia,intestinal obstruction,endolymphatic leakage,Clavien-Dindo grade Ⅰ,Ⅱ,Ⅲa,Ⅲb and Ⅳa of postoperative complications were respectively 15,1,1,1,0,3,1,2,3,0,1,3,0,3,9,1,2,0 in the anterior approach group and 25,3,0,1,2,2,2,5,7,3,2,3,1,6,14,1,2,2 in the posterior approach group,with no statistically significant difference between groups (x2=1.027,0.643,0.022,0.479,0.161,0.765,0.921,0.161,0.063,Z=-1.055,P＞0.05).Patients in 2 groups with complications were cured by symptomatic treatment.(3) Stratified analyses of surgical and postoperative situations in patients with different TNM staging,BMI and maximum tumor dimension:operation time,dissected times of lymph nodes in upper region of pancreas,cases with visible port vein,number of overall lymph node dissection,numbers of lymph node dissection in upper region of pylorus and upper region of pancreas were respectively (236.0±41.0)minutes,(33.9±6.2) minutes,32,36.0±12.0,3.8±3.0,13.4±5.5 in patients of the anterior approach group with Ⅲ stage of TNM staging and (253.0± 45.0) minutes,(36.5 ±7.0) minutes,29,31.0±t9.0,2.5±2.0,11.4±4.6 in patients of the posterior approach group with Ⅲ stage of TNM staging,with statistically significant differences between groups (t =-1.988,-2.066,x2 =4.686,t =2.472,2.757,2.016,P＜0.05).Numbers of overall lymph node dissection and number of lymph node dissection in upper region of pylorus were respectively 37.0± 12.0,3.6±3.1 in patients of the anterior approach group with BMI ≥ 25 kg/m2 and 30.0±7.0,2.0± 1.3 in patients of the posterior approach group with BMI ≥ 25 kg/m2,with statistically significant differences between groups (t =2.211,2.205,P＜0.05).Volume of intraoperative blood loss and number of lymph node dissection in upper region of pylorus were respectively (80±45) mL,4.0±2.6 in patients of the anterior approach group with maximum tumor dimension ≥ 3.3 cm and (110±67)mL,2.8± 1.8 in patients of the posterior approach group with maximum tumor dimension ≥ 3.3 cm,with statistically significant differences between groups (t =-2.320,2.589,P ＜ 0.05).(4) Follow-up and survival:of 239 patients,202 were followed up for 2-24 months,with a median time of 12 months,including 89 in the anterior approach group and 113 in the posterior approach group.During the follow-up,cases with overall survival,tumor recurrence and metastasis were respectively 85,3,8 in the anterior approach group and 109,3,11 in the posterior approach group,with no statistically significant difference between groups (x2=0.032,0.089,0.119,P＞0.05).Conclusions Both of anterior approach and posterior approach are safe and feasible in LADG,with equivalent short-term efficacies.The anterior approach in LADG has an advantage of the lymph node dissection in the upper region of pylorus compared with posterior approach,and it also is better for patients with later tumor staging,higher BMI and bigger tumor.

Objective To prepare 131I-anti-neuropilin-2-monoclonal antibody (131I-anti-NRP-2-mAb),and investigate its biodistribution and imaging in nude mice bearing xenografted lung adenocarcinoma,in order to evaluate its feasibility as an imaging agent targeting to NRP-2 positive tumors.Methods (1)131I-anti-NRP-2-mAb was prepared by Chloramine-T method under the optimum labeling conditions,then the labeling efficiency,radiochemical purity and stability were determined in vitro.(2) The binding fraction and receptor binding affinity of 131I-anti-NRP-2-mAb were measured in A549 human lung cancer cells by cell uptaking and binding experiments.(3) The A549 tumor-bearing mice were randomly divided into 4 groups with direct sampling method and were sacrificed at 6,24,48,and 72 h,respectively,after tail intravenous injection of 0.37 MBq 131I-anti-NRP-2-mAb.The distribution was measured,and the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were calculated.(4) Gamma imaging was performed in 6 mice,including 3 in the competitive inhibition control group (injected with 3.7 MBq 131I-anti-NRP-2-mAb and 100 μg atniNRP-2-mAb),at 6,24,48,and 72 h post-injection to observe the radioactivity in tumor.Two-sample t test was used for data analysis.Results (1) The labeling yield and radiochemical purity of 131I-anti-NRP-2-mAb were (94.69 ± 3.63) ％ and (98.56± 0.48) ％,respectively.The radiochemical purity was more than 85％ after incubating in phosphate-buffered solution at room temperature for 72 h.(2) At 60,120,180 and 240 min post-injection,the binding ratios of 131I-anti-NRP-2-mAb in A549 cells were (3.95±0.18)％,(5.19±0.65) ％,(6.60± 0.36) ％ and (5.58± 0.63) ％,respectively.When excessive anti-NRP-2-mAb were added,the binding ratios were reduced to (0.94±0.31)％,(1.12±0.17)％,(1.24±0.25)％ and (1.04±0.18) ％,respectively,which were significantly lower than those of non-inhibited group (t values:9.89-19.66,all P＜0.05).131I-anti-NRP-2-mAb bound to NRP-2 with high affinity half maximal inhibitory concentration (IC50 =(410.8±1.2) nmol/L).(3) Biodistribution study demonstrated that the T/M and T/B ratios increased with the time extension and were 3.83±0.18 and 1.10±0.20,respectively,at 72 h post-injection.(4) Gamma imaging studies revealed that 131I-anti-NRP-2-mAb could clearly identify A549 tumors 6 h post-injection,especially at 48 h post-injection.Tumors were not observed clearly in competitive inhibition control group.Conclusion 131I-anti-NRP-2-mAb has been successfully prepared,and it could target to NRP-2 specifically.