Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16526
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dc.contributor.authorBurvenich, Ingrid JG-
dc.contributor.authorLee, Fook-Thean-
dc.contributor.authorGuo, Nancy-
dc.contributor.authorGan, Hui K-
dc.contributor.authorRigopoulos, Angela-
dc.contributor.authorParslow, Adam C-
dc.contributor.authorO'Keefe, Graeme J-
dc.contributor.authorGong, Sylvia J-
dc.contributor.authorTochon-Danguy, Henri J-
dc.contributor.authorRudd, Stacey E-
dc.contributor.authorDonnelly, Paul S-
dc.contributor.authorKotsuma, Masakatsu-
dc.contributor.authorOhtsuka, Toshiaki-
dc.contributor.authorSenaldi, Giorgio-
dc.contributor.authorScott, Andrew M-
dc.date2016-09-25-
dc.date.accessioned2017-01-18T06:10:00Z-
dc.date.available2017-01-18T06:10:00Z-
dc.date.issued2016-09-
dc.identifier.citationTheranostics 2016; 6(12): 2225-2234en_US
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/16526-
dc.description.abstractBackground: DS-8273a, an anti-human death receptor 5 (DR5) agonistic antibody, has cytotoxic activity against human cancer cells and induces apoptosis after specific binding to DR5. DS-8273a is currently being used in clinical Phase I trials. This study evaluated the molecular imaging of DR5 expression in vivo in mouse tumor models using SPECT/CT and PET/MRI, as a tool for drug development and trial design. Methods: DS-8273a was radiolabeled with indium-111 and zirconium-89. Radiochemical purity, immunoreactivity, antigen binding affinity and serum stability were assessed in vitro. In vivo biodistribution and pharmacokinetic studies were performed, including SPECT/CT and PET/MR imaging. A dose-escalation study using a PET/MR imaging quantitative analysis was also performed to determine DR5 receptor saturability in a mouse model. Results: 111In-CHX-A″-DTPA-DS-8273a and 89Zr-Df-Bz-NCS-DS-8273a showed high immunoreactivity (100%), high serum stability, and bound to DR5 expressing cells with high affinity (Ka, 1.02-1.22 × 1010 M-1). The number of antibodies bound per cell was 32,000. In vivo biodistribution studies showed high and specific uptake of 111In-CHX-A″-DTPA-DS-8273a and 89Zr-Df-Bz-NCS-DS-8273a in DR5 expressing COLO205 xenografts, with no specific uptake in normal tissues or in DR5-negative CT26 xenografts. DR5 receptor saturation was observed in vivo by biodistribution studies and quantitative PET/MRI analysis. Conclusion: 89Zr-Df-Bz-NCS-DS-8273a is a potential novel PET imaging reagent for human bioimaging trials, and can be used for effective dose assessment and patient response evaluation in clinical trials.en_US
dc.subjectDS-8273aen_US
dc.subjectDeath receptor 5en_US
dc.subjectApoptosisen_US
dc.subjectZirconium-89en_US
dc.subjectColorectal canceren_US
dc.subjectPET/MRIen_US
dc.titleIn vitro and in vivo evaluation of 89Zr-DS-8273a as a theranostic for anti-death receptor 5 therapyen_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleTheranosticsen_US
dc.identifier.affiliationTumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australiaen_US
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Heidelberg, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Melbourne, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Medical Oncology, Austin Health, Heidelberg, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Molecular Imaging and Therapy, Austin Health, Heidelberg, Victoria, Australiaen_US
dc.identifier.affiliationSchool of Engineering and Mathematical Sciences, La Trobe University, Melbourne, Victoria, Australiaen_US
dc.identifier.affiliationSchool of Chemistry and Bio21 Molecular Science & Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australiaen_US
dc.identifier.affiliationTranslational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co Ltd, Tokyo, Japanen_US
dc.identifier.affiliationBiologics Pharmacology Research Laboratories, Daiichi Sankyo Co Ltd, Tokyo, Japanen_US
dc.identifier.affiliationDepartment of Translational Medicine and Clinical Pharmacology, Daiichi Sankyo Pharma Development, Edison, NJ, USAen_US
dc.identifier.pubmedurihttps://pubmed.ncbi.nlm.nih.gov/27924159en_US
dc.identifier.doi10.7150/thno.16260en_US
dc.type.contentTexten_US
dc.type.austinJournal Articleen_US
local.name.researcherGan, Hui K
item.openairetypeJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.fulltextNo Fulltext-
item.cerifentitytypePublications-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
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