Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/19226
Title: Molecular Imaging and Quantitation of EphA2 Expression in Xenograft Models with 89Zr-DS-8895a.
Austin Authors: Burvenich, Ingrid J G;Parakh, Sagun ;Gan, Hui K ;Lee, Fook-Thean;Guo, Nancy;Rigopoulos, Angela;Lee, Sze-Ting;Gong, Sylvia;O'Keefe, Graeme J;Tochon-Danguy, Henri;Kotsuma, Masakatsu;Hasegawa, Jun;Senaldi, Giorgio;Scott, Andrew M 
Affiliation: Translational Medicine and Clinical Pharmacology Department, Daiichi-Sankyo Co., Ltd., Tokyo, Japan
Biologics Pharmacology Research Laboratories, Daiichi-Sankyo Co., Ltd., Tokyo, Japan
Department of Translational Medicine and Clinical Pharmacology, Daiichi-Sankyo Pharma Development, Edison, New Jersey
Tumour Targeting Laboratory, Ludwig Institute for Cancer Research, Melbourne, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Australia
Department of Molecular Imaging and Therapy, Austin Health, Heidelberg, Victoria, Australia
Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine, University of Melbourne, Melbourne, Australia
Issue Date: Jun-2016
metadata.dc.date: 2016-03-03
Publication information: Journal of Nuclear Medicine 2016; 57(6): 974-980
Abstract: Subtype 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/19226
DOI: 10.2967/jnumed.115.169839
ORCID: 0000-0003-3891-2489
0000-0002-6656-295X
PubMed URL: 26940768
Type: Journal Article
Subjects: 89Zr
DS-8895a
EphA2
bioimaging
Cancer
Appears in Collections:Journal articles

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