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Molecular Imaging and Quantitation of EphA2 Expression in Xenograft Models With 89Zr-DS-8895a

Molecular Imaging and Quantitation of EphA2 Expression in Xenograft Models With 89Zr-DS-8895a

Ingrid J G Burvenich, Sagun Parakh, Hui K Gan, Fook-Thean Lee, Nancy Guo, Angela Rigopoulos, Sze-Ting Lee, Sylvia Gong, Graeme J O'Keefe, Henri Tochon-Danguy, Masakatsu Kotsuma, Jun Hasegawa, Giorgio Senaldi, etc.

J Nucl Med. 2016 Jun;57(6):974-80.

PMID: 26940768

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.
Methods:
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.
Results:
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.
Conclusion:
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413556	Monoclonal Anti-EPHA2 antibody produced in mouse			Price

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