Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/19226
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dc.contributor.authorBurvenich, Ingrid J G-
dc.contributor.authorParakh, Sagun-
dc.contributor.authorGan, Hui K-
dc.contributor.authorLee, Fook-Thean-
dc.contributor.authorGuo, Nancy-
dc.contributor.authorRigopoulos, Angela-
dc.contributor.authorLee, Sze-Ting-
dc.contributor.authorGong, Sylvia-
dc.contributor.authorO'Keefe, Graeme J-
dc.contributor.authorTochon-Danguy, Henri-
dc.contributor.authorKotsuma, Masakatsu-
dc.contributor.authorHasegawa, Jun-
dc.contributor.authorSenaldi, Giorgio-
dc.contributor.authorScott, Andrew M-
dc.date2016-03-03-
dc.date.accessioned2018-09-13T00:21:13Z-
dc.date.available2018-09-13T00:21:13Z-
dc.date.issued2016-06-
dc.identifier.citationJournal of Nuclear Medicine 2016; 57(6): 974-980-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/19226-
dc.description.abstractSubtype A2 of the erythropoietin-producing hepatocellular tyrosine kinase (EphA2) cell surface receptor is expressed in a range of epithelial cancers. This study evaluated the molecular imaging of EphA2 expression in vivo in mouse tumor models using SPECT/MR and PET/MR and a humanized anti-EphA2 antibody, DS-8895a. DS-8895a was labeled with (111)In, (125)I, and (89)Zr and assessed for radiochemical purity, immunoreactivity (Lindmo analysis), antigen-binding affinity (Scatchard analysis), and serum stability in vitro. In vivo biodistribution, imaging, and pharmacokinetic studies were performed with SPECT/MR and PET/MR. A dose-escalation study was also performed to determine EphA2 receptor saturability through tissue and imaging quantitative analysis. All conjugates demonstrated good serum stability and specific binding to EphA2-expressing cells in vitro. In vivo biodistribution studies showed high uptake of (111)In-CHX-A″-DTPA-DS-8895a and (89)Zr-Df-Bz-NCS-DS-8895a in EphA2-expressing xenograft models, with no specific uptake in normal tissues. In comparison, retention of (125)I-DS-8895a in tumors was lower because of internalization of the radioconjugate and dehalogenation. These results were confirmed by SPECT/MR and PET/MR. EphA2 receptor saturation was observed at the 30 mg/kg dose. Molecular imaging of tumor uptake of DS-8895a allows noninvasive measurement of EphA2 expression in tumors in vivo and determination of receptor saturation. (89)Zr-Df-Bz-NCS-DS-8895a is suited for human bioimaging trials on the basis of superior imaging characteristics and will inform DS-8895a dose assessment and patient response evaluation in clinical trials.-
dc.language.isoeng-
dc.subject89Zr-
dc.subjectDS-8895a-
dc.subjectEphA2-
dc.subjectbioimaging-
dc.subjectCancer-
dc.titleMolecular Imaging and Quantitation of EphA2 Expression in Xenograft Models with 89Zr-DS-8895a.-
dc.typeJournal Article-
dc.identifier.journaltitleJournal of Nuclear Medicine-
dc.identifier.affiliationTranslational Medicine and Clinical Pharmacology Department, Daiichi-Sankyo Co., Ltd., Tokyo, Japan-
dc.identifier.affiliationBiologics Pharmacology Research Laboratories, Daiichi-Sankyo Co., Ltd., Tokyo, Japan-
dc.identifier.affiliationDepartment of Translational Medicine and Clinical Pharmacology, Daiichi-Sankyo Pharma Development, Edison, New Jersey-
dc.identifier.affiliationTumour Targeting Laboratory, Ludwig Institute for Cancer Research, Melbourne, Australia-
dc.identifier.affiliationOlivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Melbourne, Australiaen
dc.identifier.affiliationDepartment of Molecular Imaging and Therapy, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Melbourne, Australiaen
dc.identifier.doi10.2967/jnumed.115.169839-
dc.identifier.orcid0000-0003-3891-2489-
dc.identifier.orcid0000-0002-6656-295X-
dc.identifier.pubmedid26940768-
dc.type.austinJournal Article-
dc.type.austinResearch Support, Non-U.S. Gov't-
local.name.researcherGan, Hui K
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptMedical Oncology-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
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