Biodistribution and pharmacokinetics of [89Zr]-anti-VEGF mAbs using PET in glioblastoma rat models,International Journal of Pharmaceutics

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Biodistribution and pharmacokinetics of [89Zr]-anti-VEGF mAbs using PET in glioblastoma rat models
International Journal of Pharmaceutics ( IF 5.3 ) Pub Date : 2024-01-13 , DOI: 10.1016/j.ijpharm.2024.123795
Lara García-Varela ₁ , Jessica Codesido ₂ , Alberto Perez-Pedrosa ₃ , María Muñoz-González ₁ , Emma Ramos-Docampo ₁ , David Rey-Bretal ₁ , Xurxo García-Otero ₁ , Noemí Gómez-Lado ₁ , Angela Turrero ₄ , Daniel Beiroa ₅ , Ana Isabel Rodríguez-Perez ₆ , Anxo Vidal ₄ , Anxo Fernández-Ferreiro ₇ , Virginia Pubul ₈ , Pablo Aguiar ₁

Affiliation

Molecular Imaging and Pharmacokinetic Modelling Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela, Spain; Nuclear Medicine and Molecular Imaging Group, Health Research Institute of Santiago de Compostela (IDIS), University Hospital Santiago de Compostela, Spain.
Molecular Imaging and Pharmacokinetic Modelling Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela, Spain; Pharmacy Dept & Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), University Hospital Santiago de Compostela, Spain.
Department of Pathology, University Hospital Ourense, Spain.
Cell Cycle and Oncology Group (CiCLOn), Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Spain.
Centro de Biomedicina Experimental (CEBEGA), University of Santiago de Compostela, Spain.
Cell and Molecular Neurobiology of Parkinson's disease, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Spain. Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
Pharmacy Dept & Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), University Hospital Santiago de Compostela, Spain.
Nuclear Medicine and Molecular Imaging Group, Health Research Institute of Santiago de Compostela (IDIS), University Hospital Santiago de Compostela, Spain.

Glioblastomas present intensive angiogenesis, thus anti–Vascular Endothelial Growth Factor (VEGF) antibodies (mAbs) have been proposed as promising therapies. However, the results of clinical trials reported moderate toxicity and limited effectiveness. This study evaluates the pharmacokinetics and biodistribution of these mAbs in a growing model of glioblastoma in rats using Positron Emission Tomography (PET). &Methods: Anti-VEGF mAbs showed 100 % Radiochemical-Purity. [Zr]-DFO-bevacizumab showed a significantly higher bioavailability in whole-blood. A significant increase in the tumor uptake was detectable at 168H PET with [Zr]-DFO-bevacizumab meanwhile with [Zr]-DFO-aflibercept it was only detectable at 336H. [Zr]-DFO-bevacizumab tumor uptake was significantly higher than that of [Zr]-DFO-aflibercept in all the scans. Tumor induction was confirmed in all animal models. MAbs detect VEGF-expression in glioblastoma models. Tumors were earlier targeted by Bevacizumab. The lower blood availability of aflibercept resulted in a lower tumor uptake than bevacizumab in all the scans.

中文翻译：

使用 PET 在胶质母细胞瘤大鼠模型中研究 [89Zr]-抗 VEGF mAb 的生物分布和药代动力学

胶质母细胞瘤呈现强烈的血管生成，因此抗血管内皮生长因子 (VEGF) 抗体 (mAb) 被认为是有前途的治疗方法。然而，临床试验结果显示毒性中等且有效性有限。本研究使用正电子发射断层扫描 (PET) 评估了这些 mAb 在胶质母细胞瘤生长模型中的药代动力学和生物分布。方法：抗 VEGF mAb 的放射化学纯度为 100%。 [Zr]-DFO-贝伐珠单抗在全血中表现出显着更高的生物利用度。使用 [Zr]-DFO-贝伐单抗在 168H PET 中可检测到肿瘤摄取显着增加，而使用 [Zr]-DFO-阿柏西普仅在 336H 时可检测到。在所有扫描中，[Zr]-DFO-贝伐单抗肿瘤摄取均显着高于[Zr]-DFO-阿柏西普。在所有动物模型中均证实了肿瘤诱导。 MAb 可检测胶质母细胞瘤模型中的 VEGF 表达。贝伐珠单抗早期针对肿瘤。在所有扫描中，阿柏西普的血液可用性较低，导致肿瘤摄取低于贝伐珠单抗。

更新日期：2024-01-13

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