1.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
2.Comparison of 99Tc m-3PRGD 2 SPECT/CT and 18F-FDG PET/CT imaging in the diagnosis of oral malignancy and cervical lymph node metastases
Meiyan LIN ; Zhenying CHEN ; Jiyun SHI ; Ke ZHENG ; Weibing MIAO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(8):482-487
Objective:To compare 99Tc m-hydrazinonicotinamide-(polyethylene glycol) 4-E((polyethylene glycol) 4-c((Arg-Gly-Asp)fK)) 2(3PRGD 2) SPECT/CT with 18F-FDG PET/CT in the evaluation of patients with oral malignancy and cervical lymph node metastases. Methods:From January 2019 to October 2019, 22 patients (16 males, 6 females; age (56.9±9.8) years) with oral malignancy who underwent both 99Tc m-3PRGD 2 SPECT/CT and 18F-FDG PET/CT at the First Affiliated Hospital of Fujian Medical University were retrospectively analyzed. The pathology was used as the gold standard, and McNemar test was used to compare the diagnostic efficacy of the two imaging methods for cervical lymph node metastases. ROC curve analysis was performed to determine the diagnostic performance for lymph node metastases. The correlation between 99Tc m-3PRGD 2 uptake and integrin α vβ 3 expression was analyzed by Spearman rank correlation analysis. Results:Both imaging modalities identified all primary tumors. Diagnostic efficiency analyses based on patient, neck side, nodal region and lymph node all showed that there were no significant differences in the sensitivity, specificity and accuracy between the two imaging modalities in diagnosing cervical metastatic lymph nodes ( χ2 values: 0-3.36, all P>0.05). The AUC of SUV max in metastatic lymph nodes detected by 99Tc m-3PRGD 2 and 18F-FDG imaging were 0.825 and 0.855, with the sensitivity, specificity and accuracy of 71.9%(23/32), 93.9%(92/98), 88.5%(115/130) and 78.1%(25/32), 93.9%(92/98), 90.0%(117/130), respectively ( χ2 values: 0.05-0.10, all P>0.05). SUV max of 99Tc m-3PRGD 2 in primary tumors and cervical metastatic lymph nodes were positively correlated with the expression of integrin α vβ 3 ( rs values: 0.58, 0.51, P values: 0.019, 0.013). Conclusion:99Tc m-3PRGD 2 SPECT/CT is a valuable diagnostic tool for oral malignancy and cervical lymph node metastases, which is comparable to 18F-FDG PET/CT.
3.Comparison of 99Tc m-3PRGD 2 SPECT/CT and 18F-FDG PET/CT imaging in the diagnosis of oral malignancy and cervical lymph node metastases
Meiyan LIN ; Zhenying CHEN ; Jiyun SHI ; Ke ZHENG ; Weibing MIAO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(8):482-487
Objective:To compare 99Tc m-hydrazinonicotinamide-(polyethylene glycol) 4-E((polyethylene glycol) 4-c((Arg-Gly-Asp)fK)) 2(3PRGD 2) SPECT/CT with 18F-FDG PET/CT in the evaluation of patients with oral malignancy and cervical lymph node metastases. Methods:From January 2019 to October 2019, 22 patients (16 males, 6 females; age (56.9±9.8) years) with oral malignancy who underwent both 99Tc m-3PRGD 2 SPECT/CT and 18F-FDG PET/CT at the First Affiliated Hospital of Fujian Medical University were retrospectively analyzed. The pathology was used as the gold standard, and McNemar test was used to compare the diagnostic efficacy of the two imaging methods for cervical lymph node metastases. ROC curve analysis was performed to determine the diagnostic performance for lymph node metastases. The correlation between 99Tc m-3PRGD 2 uptake and integrin α vβ 3 expression was analyzed by Spearman rank correlation analysis. Results:Both imaging modalities identified all primary tumors. Diagnostic efficiency analyses based on patient, neck side, nodal region and lymph node all showed that there were no significant differences in the sensitivity, specificity and accuracy between the two imaging modalities in diagnosing cervical metastatic lymph nodes ( χ2 values: 0-3.36, all P>0.05). The AUC of SUV max in metastatic lymph nodes detected by 99Tc m-3PRGD 2 and 18F-FDG imaging were 0.825 and 0.855, with the sensitivity, specificity and accuracy of 71.9%(23/32), 93.9%(92/98), 88.5%(115/130) and 78.1%(25/32), 93.9%(92/98), 90.0%(117/130), respectively ( χ2 values: 0.05-0.10, all P>0.05). SUV max of 99Tc m-3PRGD 2 in primary tumors and cervical metastatic lymph nodes were positively correlated with the expression of integrin α vβ 3 ( rs values: 0.58, 0.51, P values: 0.019, 0.013). Conclusion:99Tc m-3PRGD 2 SPECT/CT is a valuable diagnostic tool for oral malignancy and cervical lymph node metastases, which is comparable to 18F-FDG PET/CT.
4.Expert consensus on clinical application of 177Lu-prostate specific membrane antigen radio-ligand therapy in prostate cancer
Guobing LIU ; Weihai ZHUO ; Yushen GU ; Zhi YANG ; Yue CHEN ; Wei FAN ; Jianming GUO ; Jian TAN ; Xiaohua ZHU ; Li HUO ; Xiaoli LAN ; Biao LI ; Weibing MIAO ; Shaoli SONG ; Hao XU ; Rong TIAN ; Quanyong LUO ; Feng WANG ; Xuemei WANG ; Aimin YANG ; Dong DAI ; Zhiyong DENG ; Jinhua ZHAO ; Xiaoliang CHEN ; Yan FAN ; Zairong GAO ; Xingmin HAN ; Ningyi JIANG ; Anren KUANG ; Yansong LIN ; Fugeng LIU ; Cen LOU ; Xinhui SU ; Lijun TANG ; Hui WANG ; Xinlu WANG ; Fuzhou YANG ; Hui YANG ; Xinming ZHAO ; Bo YANG ; Xiaodong HUANG ; Jiliang CHEN ; Sijin LI ; Jing WANG ; Yaming LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(5):844-850,封3
177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.
5.Spatiotemporal characteristics of hand,foot and mouth disease and influencing factors in China from 2011 to 2018.
Ya Ting WANG ; Wen Jia PENG ; Hua Lin SU ; Weibing WANG
Chinese Journal of Epidemiology 2022;43(10):1562-1567
Objective: To analyze the spatiotemporal characteristics of hand,foot and mouth disease (HFMD) in China, explore the association of socioeconomic, population and health services factors with the incidence of HFMD in China, and provide information for the prevention and control of HFMD. Methods: Bayesian spatiotemporal model was used to fit the data of HFMD, evaluate the spatiotemporal variation of HFMD, and identify the potential association between the risk of HFMD and social, economic, population and health services. Results: From 2011 to 2018, a total of 17 118 050 HFMD cases, including 2 283 deaths, were reported in China. The reported incidence showed a fluctuating increase trend from 2011 to 2014, and a fluctuating decrease trend from 2014 to 2018. Meanwhile, there was a fluctuating decrease trend of mortality rate. The incidence of HFMD had spatial clustering, with the highest incidence in southern China with hot spot and high risk areas, and the lowest incidence in northwestern China where cold spot and low risk areas were found. The risk for HFMD was associated with GDP per capita (RR=3.54), number of industrial enterprises above designated size of 10 000 people (RR=1.61), urbanization rate (RR=3.00), birth rate (RR=2.36), number of beds in medical institutions per 10 000 people (RR=3.40), and green area in parks per capita (RR=0.57). Conclusions: The hotspot area for HFMD prevention and control in China was in the southeast coastal provinces from 2011 to 2018. In order to reduce the incidence of HFMD, it is necessary to increase the green area in parks per capita while accelerating urbanization process.
Humans
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Animals
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Bayes Theorem
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Foot-and-Mouth Disease
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China/epidemiology*
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Hand, Foot and Mouth Disease/epidemiology*
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Menthol
6.Implementing and evaluating the online course system of orthodontic education
Luwei LIU ; Weibing ZHANG ; Wei ZHANG ; Xiaoqing LU ; Bin YAN ; Lin WANG
Chinese Journal of Stomatology 2021;56(3):279-282
A new teaching mode with the combination of online teaching and flipped class was designed and implemented in the Stomatological College of Nanjing Medical University based on the National Online Open Courses, the Virtual Interactive Network Teaching Platform and the E-learning Network Teaching Platform. The new online course system of orthodontic education was constructed with several components including the process and outcome assessments, the professional literature and knowledge summary reports and the virtual interactive online training. With the informative and convenient online teaching resources and modes, students′ comprehensive abilities of independent learning were improved.
7.Spatial scan analysis on tuberculosis notifications in Zhejiang province, 2005-2014
Wenming CHEN ; Yu ZHANG ; Lin ZHOU ; Bin CHEN ; Songhua CHEN ; Weibing WANG ; Xiaomeng WANG
Chinese Journal of Infectious Diseases 2017;35(2):88-92
Objective To analyze the epidemic characteristics of tuberculosis (TB) cases in Zhejiang province from 2005 to 2014, and to identify the cluster spots.Methods TB notification data in Zhejiang province from 2005 to 2014 were analyzed at county and district level by using spatial scan statistic analysis method, which was showed on the digital map.Results In zhejiang province from 2005 to 2014, a total of 377 707 cases of patients with tuberculosis were reported.The average annual registration rates of the entire province was 72.61/100 000 (range: 28.85/100 000-182.90/100 000).Spatial analysis identified 14 clusters (RR=1.05-1.62) with statistical significance.Temporal analysis revealed that there were clusters between 2005 and 2009 in terms of the notification data on TB cases (RR=1.27,P=0.001).Spatio-temporal analysis identified 6 clusters (RR=1.19-3.55) with statistical significance.Counties and districts included in the first class cluster were similar by using the two different methods-spatial analysis and spatial-temporal analysis.Conclusions There is a descending trend of TB cases notification rates from western to eastern Zhejiang during the study period.The distribution of the TB case notified is not random at spatial, temporal and spatio-temporal levels.
8.Acteoside promotes proliferation of neural stem cells from adult mice by activating PI3 K/AKT pathway
Huimin LIN ; Weibing DUAN ; Rui SHAO ; Lifeng HAN ; Yan ZHU ; Xiumei GAO ; Yu WANG
Chinese Pharmacological Bulletin 2016;32(6):836-840
Aim Toclarifytheeffectofacteosideon proliferation of neural stem cells (NSCs ) from adult mice,as well as the involved signaling pathway.Meth-ods NSCswereisolatedfromthesubventricularzone (SVZ)of adult C57BL/6 mice,then identified by im-munofluorescence staining with Nestin,the marker of NSCs.NSCs were exposed to acteoside (5,10,20,40μmol·L-1 )in absence of mitogen(EGF/bFGF)for 24 h.We employed CCK8 assay to detect NSCs viability and BrdU staining to identify NSCs proliferation.We performed Western blot to quantify the expression level ofp-AktinducedbyacteosideonNSCs.Results With-out mitogen,acteoside increased NSCs proliferation by activating p-Akt,which can be blocked by LY294002, the inhibitor of PI3K/AKT signaling pathway.Conclu-sion ActeosidepromotestheproliferationofNSCsfrom adult mice by activating PI3K/AKT pathway.
9.Spatial distribution characteristics analysis on multidrug-resistant tuberculosis cases in Zhejiang province, 2010-2012
Wenming CHEN ; Xiaomeng WANG ; Bin CHEN ; Songhua CHEN ; Lin ZHOU ; Shengnan WANG ; Weibing WANG
Chinese Journal of Epidemiology 2016;37(6):831-835
Objective To analyze the spatial distribution characteristics ofmultidrug-resistant (MDR) tuberculosis (TB) cases in Zhejiang province in 2010-2012.Methods Data on MDR-TB cases in Zhejiang province were collected and linked to the digital map at the county and district levels.ArcGIS 10.0 software was used for spatial analysis.Results Results from the spatial autocorrelation analysis showed that spatial aggregation appeared in MDR-TB distribution during 2010-2012 while local Moran's I spatial autocorrelation analysis identified several "high incidence regions" (Wuxing,Deqing,Yuhang,Gongshu,Jianggan,Xiaoshan,Yuecheng,Shaoxing Shengzhou,Changshan,Kecheng),and "low incidence region" (Haishu).Through Getis-Ord General G spatial autocorrelation analysis,18 "positive hotspots" (Wuxing,Nanxun,Deqing,Yuhang,Shangcheng,Xiacheng,Gongshu,Jianggan,Binjiang Xiaoshan Xihu,Haining,Yuecheng,Shaoxing,Zhuji,Shengzhou,Kecheng and Suichang) and 11 "negative hotspots" (Nanhu,Haiyan,Cixi,Dinghai,Zhenhai,Jiangbei,Jiangdong,Beilun,Yinzhou,Fenghua,and Yueqing) were identified.Conclusions Spatial analysis on MDR-TB incidence implied the spatial aggregation in Zhejiang province.Data showed that the hotspots with high population density and human movement were under progressive expansion.
10.Integration of spatial epidemiology and molecular epidemiology used for study on tuberculosis
Wenming CHEN ; Qingrong ZHOU ; Xiaomeng WANG ; Huishu MAO ; Ping WANG ; Lin ZHOU ; Weibing WANG
Chinese Journal of Epidemiology 2016;37(12):1683-1686
Spatial epidemiology and molecular epidemiology have been widely used in the studies of tuberculosis (TB),but each with limitations.Integration of the two methods provides new ideas and methods in TB research.All referenced articles are from CNKI,Wan Fang database,PubMed database and Web of Science database.Method of combining spatial epidemiology and molecular epidemiology has been widely used in determining the local epidemic strains of TB genotype,the transmission mechanism,risk factors of TB,drug-resistant TB,as well as evaluating the effectiveness of TB prevention and control measures.Application of the combined methods is of important significance in the studies of TB,thus worthy to be further introduced to researchers and disease prevention and control workers in this country.

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