In Vivo Preclinical Assessment of the VEGF Targeting Potential of the Newly Synthesized [52Mn]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

doi:10.3390/diagnostics13020236

In Vivo Preclinical Assessment of the VEGF Targeting Potential of the Newly Synthesized [⁵²Mn]Mn-DOTAGA-Bevacizumab Using Experimental Cervix Carcinoma Mouse Model

Diagnostics (Basel). 2023 Jan 8;13(2):236. doi: 10.3390/diagnostics13020236.

Authors

Csaba Csikos^{1

2}, Adrienn Vágner³, Gábor Nagy³, Ibolya Kálmán-Szabó¹, Judit P Szabó¹, Minh Toan Ngo^{1

2}, Zoltán Szoboszlai³, Dezső Szikra¹, Zoárd Tibor Krasznai⁴, György Trencsényi^{1

2}, Ildikó Garai^{1

2

3}

Affiliations

¹ Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
² Gyula Petrányi Doctoral School of Clinical Immunology and Allergology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
³ Scanomed Ltd., H-4032 Debrecen, Hungary.
⁴ Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.

Abstract

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.

Keywords: 52Mn; VEGF; bevacizumab; cervix carcinoma; positron emission tomography.

Grants and funding

This research work was conducted with the support of the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation (C.C. and G.T.) The published work was supported by the EFOP-3.6.3-VEKOP-16-2017-00009 fund of the European Union, by the NKFIH K119552 grant of the European Social Fund and National Research, Development, and Innovation Office, and by the Thematic Excellence Programme (TKP2020-NKA-04) of the Ministry for Innovation and Technology in Hungary. This research was also supported by the KDP-2021 program of the Ministry for Innovation and Technology from the source of the national research, development, and innovation fund (G.T. and I.K.-S.).