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

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

作者信息

Csikos Csaba, Vágner Adrienn, Nagy Gábor, Kálmán-Szabó Ibolya, Szabó Judit P, Ngo Minh Toan, Szoboszlai Zoltán, Szikra Dezső, Krasznai Zoárd Tibor, Trencsényi György, Garai Ildikó

机构信息

Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.

Gyula Petrányi Doctoral School of Clinical Immunology and Allergology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.

出版信息

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

DOI:10.3390/diagnostics13020236
PMID:36673046
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9858384/
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., Mn) 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 Mn-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, [Mn]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.

摘要

在人源化单克隆抗体中，贝伐单抗特异性结合血管内皮生长因子A（VEGF-A）。VEGF-A是宫颈癌中一种过度表达的生物标志物，参与肿瘤相关新生血管的形成和维持。使用放射性标记的靶向特异性抗体的非侵入性正电子发射断层扫描（免疫PET）可对肿瘤靶点表达进行纵向和定量评估。由于抗体具有较长的循环时间，半衰期较长的放射性金属离子（如锰）是同位素偶联的最佳选择。我们临床前研究的目的是评估锰标记的DOTAGA-贝伐单抗的生物分布和肿瘤靶向潜力。通过使用表达VEGF-A的KB-3-1（人宫颈癌）荷瘤CB17 SCID小鼠模型和体内PET/MRI成像，评估了这种新型免疫PET配体的VEGF-A靶向潜力。由于在皮下定位的实验性宫颈癌肿瘤中发现了高度特异性的聚集，[锰]锰-DOTAGA-贝伐单抗是一种有前景的PET探针，可用于检测VEGF-A阳性妇科肿瘤、患者选择以及监测靶向血管生成治疗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/bc927ec60b23/diagnostics-13-00236-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/ff8826912a0b/diagnostics-13-00236-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/5abcf6662db5/diagnostics-13-00236-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/9e28216ae888/diagnostics-13-00236-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/a4fbb56facc8/diagnostics-13-00236-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/313ac7b3542e/diagnostics-13-00236-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/bc927ec60b23/diagnostics-13-00236-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/ff8826912a0b/diagnostics-13-00236-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/5abcf6662db5/diagnostics-13-00236-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/9e28216ae888/diagnostics-13-00236-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/a4fbb56facc8/diagnostics-13-00236-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/313ac7b3542e/diagnostics-13-00236-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00dd/9858384/bc927ec60b23/diagnostics-13-00236-g006.jpg

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