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

使用实验性宫颈癌小鼠模型对新合成的 [52Mn]Mn-DOTAGA-贝伐单抗的 VEGF 靶向潜力进行体内临床前评估

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作者: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

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.

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