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dc.contributor.authorBurvenich, Ingrid J G-
dc.contributor.authorGoh, Yit Wooi-
dc.contributor.authorGuo, Nancy-
dc.contributor.authorGan, Hui K-
dc.contributor.authorRigopoulos, Angela-
dc.contributor.authorCao, Diana-
dc.contributor.authorLiu, Zhanqi-
dc.contributor.authorAckermann, Uwe-
dc.contributor.authorWichmann, Christian Werner-
dc.contributor.authorMcDonald, Alexander Franklin-
dc.contributor.authorHuynh, Nhi-
dc.contributor.authorO'Keefe, Graeme Joseph-
dc.contributor.authorGong, Sylvia Jie-
dc.contributor.authorScott, Fiona Elizabeth-
dc.contributor.authorLi, Linghui-
dc.contributor.authorGeng, Wanping-
dc.contributor.authorZutshi, Anup-
dc.contributor.authorLan, Yan-
dc.contributor.authorScott, Andrew M-
dc.identifier.citationEuropean Journal of Nuclear Medicine and Molecular Imaging 2021; 48(10): 3075-3088en
dc.description.abstractΤhis study aimed to optimize the 89Zr-radiolabelling of bintrafusp alfa investigational drug product and controls, and perform the in vitro and in vivo characterization of 89Zr-Df-bintrafusp alfa and 89Zr-Df-control radioconjugates. Bintrafusp alfa (anti-PD-L1 human IgG1 antibody fused to TGF-β receptor II (TGF-βRII), avelumab (anti-PD-L1 human IgG1 control antibody), isotype control (mutated inactive anti-PD-L1 IgG1 control antibody), and trap control (mutated inactive anti-PD-L1 human IgG1 fused to active TGF-βRII) were chelated with p-isothiocyanatobenzyl-desferrioxamine (Df). After radiolabelling with zirconium-89 (89Zr), radioconjugates were assessed for radiochemical purity, immunoreactivity, antigen binding affinity, and serum stability in vitro. In vivo biodistribution and imaging studies were performed with PET/CT to identify and quantitate 89Zr-Df-bintrafusp alfa tumour uptake in a PD-L1/TGF-β-positive murine breast cancer model (EMT-6). Specificity of 89Zr-Df-bintrafusp alfa was assessed via a combined biodistribution and imaging experiment in the presence of competing cold bintrafusp alfa (1 mg/kg). Nanomolar affinities for PD-L1 were achieved with 89Zr-Df-bintrafusp alfa and 89Zr-avelumab. Biodistribution and imaging studies in PD-L1- and TGF-β-positive EMT-6 tumour-bearing BALB/c mice demonstrated the biologic similarity of 89Zr-Df-bintrafusp alfa and 89Zr-avelumab indicating the in vivo distribution pattern of bintrafusp alfa is driven by its PD-L1 binding arm. Competition study with 1 mg of unlabelled bintrafusp alfa or avelumab co-administered with trace dose of 89Zr-labelled bintrafusp alfa demonstrated the impact of dose and specificity of PD-L1 targeting in vivo. Molecular imaging of 89Zr-Df-bintrafusp alfa biodistribution was achievable and allows non-invasive quantitation of tumour uptake of 89Zr-Df-bintrafusp alfa, suitable for use in bioimaging clinical trials in cancer patients.en
dc.subjectBintrafusp alfaen
dc.titleRadiolabelling and preclinical characterization of 89Zr-Df-radiolabelled bispecific anti-PD-L1/TGF-βRII fusion protein bintrafusp alfa.en
dc.typeJournal Articleen
dc.identifier.journaltitleEuropean Journal of Nuclear Medicine and Molecular Imagingen
dc.identifier.affiliationEMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany, Billerica, MA, USAen
dc.identifier.affiliationOlivia Newton-John Cancer Research Instituteen
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Melbourne, Australiaen
dc.identifier.affiliationMolecular Imaging and Therapyen
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Melbourne, Australiaen
dc.identifier.affiliationSchool of Engineering and Mathematical Sciences, La Trobe University, Melbourne, Australiaen
dc.identifier.pubmedid33608805, Uwe
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
item.grantfulltextnone- Oncology- Newton-John Cancer Wellness and Research Centre- Imaging and Therapy- Imaging and Therapy- Newton-John Cancer Research Institute-
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