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典型文献
Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer
文献摘要:
Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,68Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95%and radiochemical purity of 97%.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NC1-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.
文献关键词:
作者姓名:
Yinfei Chen;Shiyu Zhu;Jiayu Fu;Jianguo Lin;Yan Sun;Gaochao Lv;Minhao Xie;Tao Xu;Ling Qiu
作者机构:
NHC Key Laboratory of Nuclear Medicine,Jiangsu Key Laboratory of Molecular Nuclear Medicine,Jiangsu Institute of Nuclear Medicine,Wuxi,Jiangsu,214063,China;Department of Radiopharmaceuticals,School of Pharmacy,Nanjing Medical University,Nanjing,211166,China;Smart Nuclide Biopharma Co.,Ltd.,Suzhou,Jiangsu,215123,China
引用格式:
[1]Yinfei Chen;Shiyu Zhu;Jiayu Fu;Jianguo Lin;Yan Sun;Gaochao Lv;Minhao Xie;Tao Xu;Ling Qiu-.Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer)[J].药物分析学报(英文),2022(06):869-878
A类:
Nb109,NODA
B类:
Development,radiolabeled,site,single,domain,antibody,positron,emission,tomography,probe,monitoring,L1,expression,Despite,advances,immunotherapy,treatment,cancers,patients,benefit,from,programmed,death,ligand,immune,checkpoint,blockade,Anti,therapeutic,effects,reportedly,correlate,hence,detection,guide,achieve,better,Therefore,affinity,new,specifically,tracer,68Ga,cysteine,aspartic,acid,valine,CDV,was,designed,synthesized,accurately,obtained,using,conjugation,strategy,radiochemical,yield,about,purity,It,showed,dissociation,constant,nM,Both,uptake,assay,PET,imaging,revealed,higher,positive,A375,hPD,U87,tumor,cells,than,negative,Meanwhile,NC1,H1299,xenograft,indicated,that,doxorubicin,could,upregulate,allowing,timely,interventional,In,conclusion,this,sensitively,dynamically,changes,levels,different,help,screen,who
AB值:
0.539558
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