亚洲免费av电影一区二区三区,日韩爱爱视频,51精品视频一区二区三区,91视频爱爱,日韩欧美在线播放视频,中文字幕少妇AV,亚洲电影中文字幕,久久久久亚洲av成人网址,久久综合视频网站,国产在线不卡免费播放

        ?

        Comment on: “Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors”

        2023-12-30 07:40:50CuicuiLiXiaoyuanChenJingjingZhang
        Journal of Pharmaceutical Analysis 2023年9期

        Cuicui Li ,Xiaoyuan Chen ,Jingjing Zhang

        a Department of Diagnostic Radiology,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,119074,Singapore

        b Clinical Imaging Research Centre,Centre for Translational Medicine,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,117599,Singapore

        c Department of Nuclear Medicine,Beijing Friendship Hospital Affiliated to Capital Medical University,Beijing,100050,China

        d Nanomedicine Translational Research Program,Yong Loo Lin School of Medicine,National University of Singapore,Singapore,117597,Singapore

        e Departments of Surgery,Chemical and Biomolecular Engineering,and Biomedical Engineering,Yong Loo Lin School of Medicine and College of Design and Engineering,National University of Singapore,Singapore,119074,Singapore

        f Institute of Molecular and Cell Biology,Agency for Science,Technology,and Research (A*STAR),61 Biopolis Drive,Proteos,Singapore,138673,Singapore

        In the ever-evolving landscape of cancer research and treatment,the quest for novel and non-invasive imaging techniques has become crucial for accurate diagnosis and effective therapy.This study [1] successfully developed a good manufacturing practices(GMP) grade89Zr-labeled anti-Claudin18.2 (CLDN18.2) recombinant humanized antibody TST001.89Zr-DFO-TST001 exhibited high radiochemical purity(>99%)and specific activity(24.15±1.34 GBq/μmol).It demonstrated good specificity and rapid tumor accumulation in vivo and in vivo.Through immuno-PET imaging,it enables non-invasive visualization and quantification of CLDN18.2 expression level in CLDN18.2-positive gastrointestinal tumor models.

        CLDN18.2 is a member of the tight junction protein family of CLDN18,which plays a critical role in regulating tissue permeability,paracellular transport,and signal transduction processes.Research has revealed that CLDN18.2 is predominantly expressed in the gastric mucosa and is retained during malignant transformation.CLDN18.2 demonstrates high expression levels in various cancers,particularly in gastrointestinal cancers,while its expression in normal healthy tissues is limited,making it a potential target for cancer theranostics [2].With the development of precision medicine,immunotherapy has achieved great success.Recently published Phase III clinical trial data demonstrated that in patients with CLDN18.2-positive,HER2-negative,locally advanced unresectable,or metastatic gastric or gastroesophageal junction adenocarcinoma,immunotherapy targeting CLDN18.2 using zolbetuximab combined with mFOLFOX6 treatment significantly prolonged median progression-free survival (10.61 months vs.8.67 months) and median overall survival(18.23 months vs.15.54 months)compared with placebo plus mFOLFOX6 treatment [3].The TST001 antibody used in this study was less fucosylated and demonstrated more potent complement-dependent cytotoxicity (CDC) and antibodydependent cellular phagocytosis (ADCP) in CLDN18.2-positive cells and patient-derived xenograft models than zolbetuximab [4].This study is also the first published article on the use of radiolabeled TST001 for immuno-PET imaging in gastrointestinal tumor models.

        As mentioned in the article [1],the current main detection methods of CLDN18.2 protein,such as immunohistochemistry(IHC),are invasive,and due to the heterogeneity of tumors,they cannot provide real-time comprehensive information about the distribution and expression levels of CLDN18.2 in patients.Immuno-PET imaging is a specific molecular imaging technique newly developed in recent years,which uses radiolabeled specific monoclonal antibodies or their fragments as molecular tracer probes.Immuno-PET combines the high specificity and affinity of antibody targeting with the high sensitivity and quantitative analysis of PET imaging,allowing non-invasive visualization and evaluation of target antigen expression and distribution in vivo,By facilitating precise diagnosis,staging,and monitoring of treatment response,immuno-PET emerges as a highly promising imaging modality with great application potential.In this study,89Zr-DFOTST001 was used to detect the expression and distribution of CLDN18.2 in gastrointestinal tumors.This novel molecular probe holds promise as a tool for the screening of beneficiary groups and efficacy evaluation of CLDN18.2 targeted therapy.

        Although89Zr-DFO-TST001 allows visualization and precise quantification of tumor CLDN18.2 expression,some limitations remain.Due to the large molecular weight of intact monoclonal antibodies (about 150 kDa),the circulation and retention time of89Zr-DFO-TST001 in vivo are prolonged,resulting in a peak tumor uptake occurring several days post injection (p.i.) (48 h p.i.in this study).Additionally,the imaging agent is primarily eliminated through the liver,leading to significant hepatic radioactivity accumulation,which significantly affects the diagnostic accuracy of liver metastases.In another study published by the same team,it was observed that the tumor-to-liver ratios of the124I-labeled humanized anti-CLDN18.2 antibody 18B10(10L) and124I/Cy5.5-labeled murine anti-CLDN18.2 antibody 5C9,were significantly higher than that reported here[5,6].It is unclear whether such discrepancy comes from the differences in radiolabels and/or the antibodies.

        Wei et al.[7]used positron-emitting radionuclide-labeled anti-CLDN18.2 nanobody (12-15 kDa;the variable region of the heavy chain of heavy chain-only antibody [VHH]) and found significant accumulation of radioactivity in tumors 1 h p.i..But due to the small molecular weight,it resulted in a heavy burden on the kidneys.The anti-CLDN18.2 VHH-Fc developed by Hu et al.[8]and the hu7v3-Fc developed by Zhong et al.[9](recombinant VHH fused with human IgG1-Fc),were labeled with89Zr and imaged in CLDN18.2-positive tumor models,with persistent tumor radioactivity accumulation and favorable tumor-to-liver ratios.Antibody fragments such as F(ab')2and Fab labeled with radionuclides can be used instead of intact antibodies to prepare molecular probes,which can reduce the molecular weight to 110 kDa and 50 kDa while retaining the specific binding of antigen-antibody.This not only avoids the interference of the Fc region with the immune system but also allows faster pharmacokinetic properties [10].It might be possible that in this case,the use of radiolabeled antibody fragments instead of intact antibodies will solve the issue of low tumor-to-liver ratio.

        Overall,the development of a CLDN18.2-targeting immuno-PET probe represents a significant advancement in non-invasive imaging for gastrointestinal tumors and other CLDN18.2-positive tumors.Based on the favorable anti-tumor efficacy and relatively low toxicity of TST001 antibody observed in CLDN18.2-positive cells and patients [4],it is possible to identify patients with high expression of CLDN18.2 as potential candidates through immuno-PET for subsequent radioimmunotherapy,such as177Lu-labeled TST001.This approach may provide a novel treatment option for cancer patients who are intolerant to chemotherapy or require repeated administration in the future.

        Declaration of competing interest

        The authors declare that there are no conflicts of interest.

        Acknowledgments

        This work was supported by the National University of Singapore (Grant Nos.: NUHSRO/2021/097/Startup/13,NUHSRO/2020/133/Startup/08,NUHSRO/2023/008/NUSMed/TCE/LOA,NUHSRO/2021/034/TRP/09/Nanomedicine,and NUHSRO/2021/044/Kickstart/09/LOA),National Medical Research Council (Grant Nos.:OFYIRG23jan-0025,OFYIRG23jan-0017,MOH-001254-01,and CG21APR1005),Singapore Ministry of Education Academic Research Fund (Grant Nos.: NUHSRO/2022/093/T1/Seed-Sep/06 and MOE-000387-01),National Research Foundation (Grant No.:CRP28-2022RS-0001),National Natural Science Foundation of China (Grant No.: 82202206),and Beijing Natural Science Foundation (Grant No.:7224365).

        av一区二区三区人妻少妇| 亚洲国产成人久久精品美女av| 91乱码亚洲精品中文字幕| 99久久婷婷国产亚洲终合精品 | 欧美成人午夜免费影院手机在线看 | 日韩精品第一区二区三区| 熟妇熟女乱妇乱女网站| 少妇人妻偷人精品视频| 毛片av在线播放亚洲av网站| 青青草手机成人自拍视频| 中文字幕一区二区综合| 日韩欧美aⅴ综合网站发布| 国产人妻精品一区二区三区| 免费国产一级特黄aa大片在线| 青青草视频在线你懂的| 一本久久精品久久综合| 国产成人av乱码在线观看| 日韩精品一区二区三区免费视频 | 亚洲日韩国产精品不卡一区在线 | 国产成人久久777777| 日本嗯啊在线观看| 中文字幕东京热一区二区人妻少妇| 国产亚洲精品综合一区| 激情影院内射美女| 少妇无码av无码去区钱| 91麻豆精品激情在线观最新| 亚洲高清在线免费视频| 精品少妇一区二区三区免费观 | 亚洲色AV天天天天天天| 在线观看二区视频网站二区| 精品国产三级a∨在线欧美| 色噜噜狠狠一区二区三区果冻| 国产高清国内精品福利99久久| 日本视频一区二区三区三州| 日韩中文字幕有码午夜美女| 亚洲成在人网站av天堂| 日批视频免费在线观看| 国产视频一区二区三区在线看| 国产亚洲自拍日本亚洲 | 少妇高清精品毛片在线视频| 亚洲中文字幕乱码免费|