In Vivo Preclinical Assessment of the VEGF Targeting Potential of the Newly Synthesized [<sup>52</sup>Mn]Mn-DOTAGA-Bevacizumab Using Experimental Cervix Carcinoma Mouse Model
Csaba Csikos,
Adrienn Vágner,
Gábor Nagy,
Ibolya Kálmán-Szabó,
Judit P. Szabó,
Minh Toan Ngo,
Zoltán Szoboszlai,
Dezső Szikra,
Zoárd Tibor Krasznai,
György Trencsényi,
Ildikó Garai
Affiliations
Csaba Csikos
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Adrienn Vágner
Scanomed Ltd., H-4032 Debrecen, Hungary
Gábor Nagy
Scanomed Ltd., H-4032 Debrecen, Hungary
Ibolya Kálmán-Szabó
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Judit P. Szabó
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Minh Toan Ngo
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Zoltán Szoboszlai
Scanomed Ltd., H-4032 Debrecen, Hungary
Dezső Szikra
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Zoárd Tibor Krasznai
Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
György Trencsényi
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Ildikó Garai
Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Among humanized monoclonal antibodies, bevacizumab specifically binds to vascular endothelial growth factor A (VEGF-A). VEGF-A is an overexpressed biomarker in cervix carcinoma and is involved in the development and maintenance of tumor-associated neo-angiogenesis. The non-invasive positron emission tomography using radiolabeled target-specific antibodies (immuno-PET) provides the longitudinal and quantitative assessment of tumor target expression. Due to antibodies having a long-circulating time, radioactive metal ions (e.g., 52Mn) with longer half-lives are the best candidates for isotope conjugation. The aim of our preclinical study was to assess the biodistribution and tumor-targeting potential of 52Mn-labeled DOTAGA-bevacizumab. The VEGF-A targeting potential of the new immuno-PET ligand was assessed by using the VEGF-A expressing KB-3-1 (human cervix carcinoma) tumor-bearing CB17 SCID mouse model and in vivo PET/MRI imaging. Due to the high and specific accumulation found in the subcutaneously located experimental cervix carcinoma tumors, [52Mn]Mn-DOTAGA-bevacizumab is a promising PET probe for the detection of VEGF-A positive gynecological tumors, for patient selection, and monitoring the efficacy of therapies targeting angiogenesis.
