放射免疫疗法
多塔
医学
体内分布
体内
黑色素瘤
显像剂
药代动力学
癌症研究
单克隆抗体
药理学
抗体
化学
贝伐单抗
体外
化疗
内科学
免疫学
生物
生物技术
生物化学
作者
Ximena Camacho,Victoria Calzada,Marcelo Fernández,Ómar Alonso,Roger Chammas,Eloísa Riva,Juan Gambini,Pablo Cabral
出处
期刊:Current Radiopharmaceuticals
[Bentham Science]
日期:2017-04-01
卷期号:10 (1): 21-28
被引量:5
标识
DOI:10.2174/1874471009666161010155246
摘要
Background: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. Objective: To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Methods: Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. Results: DOTA-Bevacizumab was efficiently labeled with 177LuCl3 at 37 °C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of 177Lu-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of 177Lu-DOTA-Bevacizumab at 24 h. Conclusions: Our results support the potential role of 177Lu-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease.
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