PT - JOURNAL ARTICLE AU - Ingrid J.G. Burvenich AU - Sagun Parakh AU - Hui K. Gan AU - Fook-Thean Lee AU - Nancy Guo AU - Angela Rigopoulos AU - Sze-Ting Lee AU - Sylvia Gong AU - Graeme J. O’Keefe AU - Henri Tochon-Danguy AU - Masakatsu Kotsuma AU - Jun Hasegawa AU - Giorgio Senaldi AU - Andrew M. Scott TI - Molecular Imaging and Quantitation of EphA2 Expression in Xenograft Models with <sup>89</sup>Zr-DS-8895a AID - 10.2967/jnumed.115.169839 DP - 2016 Jun 01 TA - Journal of Nuclear Medicine PG - 974--980 VI - 57 IP - 6 4099 - http://jnm.snmjournals.org/content/57/6/974.short 4100 - http://jnm.snmjournals.org/content/57/6/974.full SO - J Nucl Med2016 Jun 01; 57 AB - 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. Methods: DS-8895a was labeled with 111In, 125I, and 89Zr 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. Results: All conjugates demonstrated good serum stability and specific binding to EphA2-expressing cells in vitro. In vivo biodistribution studies showed high uptake of 111In-CHX-A″-DTPA-DS-8895a and 89Zr-Df-Bz-NCS-DS-8895a in EphA2-expressing xenograft models, with no specific uptake in normal tissues. In comparison, retention of 125I-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. Conclusion: Molecular imaging of tumor uptake of DS-8895a allows noninvasive measurement of EphA2 expression in tumors in vivo and determination of receptor saturation. 89Zr-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.