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Oncotarget. 2017 Sep 15. doi: 10.18632/oncotarget.20914. pii: 20914. pmc: PMC5669955

Development of a radiolabeled caninized anti-EGFR antibody for comparative oncology trials.

Fazekas-Singer J¹, Berroterán-Infante N², Rami-Mark C³, Dumanic M⁴, Matz M⁵, Willmann M⁶, Andreae F⁷, Singer J⁸, Wadsak W⁹, Mitterhauser M¹⁰, Jensen-Jarolim E¹¹

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¹Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna, and University of Vienna, Vienna, Austria.
²Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
³Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
⁴Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
⁵Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
⁶Department for Companion Animals and Horses, University of Veterinary Medicine Vienna, Vienna, Austria.
⁷piCHEM Forschungs- und Entwicklungs GmbH, Graz, Austria.
⁸Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
⁹Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
¹⁰Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
¹¹Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna, and University of Vienna, Vienna, Austria.

Abstract

Due to large homology of human and canine EGFR, dogs suffering from spontaneous EGFR+ cancer can be considered as ideal translational models. Thereby, novel immunotherapeutic compounds can be developed for both human and veterinary patients. This study describes the radiolabeling of a canine anti-EGFR IgG antibody (can225IgG) with potential diagnostic and therapeutic value in comparative clinical settings. Can225IgG was functionalized with DTPA for subsequent chelation with the radionuclide (99m)Tc. Successful coupling of 10 DTPA molecules per antibody on average was proven by significant mass increase in MALDI-TOF spectroscopy, gel electrophoresis and immunoblots. Following functionalization and radiolabeling, (99m)Tc-DTPA-can225IgG fully retained its binding capacity towards human and canine EGFR in flow cytometry, immuno- and radioblots, and autoradiography. The affinity of radiolabeled can225IgG was determined to KD 0.8 ±0.0031 nM in a real-time kinetics assay on canine carcinoma cells by a competition binding technique. Stability tests of the radiolabeled compound identified TRIS buffered saline as the ideal formulation for short-term storage with 87.11 ±6.04% intact compound being still detected 60 minutes post radiolabeling. High stability, specificity and EGFR binding affinity pinpoint towards (99m)Tc-radiolabeled can225IgG antibody as an ideal lead compound for the first proof-of-concept diagnostic and therapeutic applications in canine cancer patients.

KEYWORDS: canine antibody, canine mammary carcinoma, comparative oncology, epidermal growth factor receptor, radio-immunotherapy

Publikations ID: 29137329
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