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 99mTc. 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, 99mTc-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 99mTc-radiolabeled can225IgG antibody as an ideal lead compound for the first proof-of-concept diagnostic and therapeutic applications in canine cancer patients.
Highlights
Detection of primary and secondary malignant lesions in clinical oncology currently largely depends on tracking of the first steps in glycolysis in metabolically active tissue via 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in PET or PET/CT [1, 2]
epidermal growth factor receptor-1 (EGFR)-overexpression is reported amongst others in colorectal cancer or carcinomas of the head and neck region and highly successfully targeted by specific immunotherapy with the monoclonal antibody cetuximab [5]
Decisions for patient stratification in clinical oncology heavily depend on histopathology
Summary
Detection of primary and secondary malignant lesions in clinical oncology currently largely depends on tracking of the first steps in glycolysis in metabolically active tissue via 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in PET or PET/CT [1, 2]. Under certain circumstances, this method can display false positive results, e.g. in inflamed tissue [3] or highly metabolizing healthy tissues like brain or liver [4]. Tumor specific detection with monoclonal antibodies targeting tumor-associated antigens (TAAs) offers an ideal, refined target for novel therapeutic and diagnostic (=theranostic) strategies. Besides the diagnostic potency of radiolabeled antibodies, their therapeutic value in cancer has been recognized under the concept of theranostics [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
