Lu-177-DOTA- Bevacizumab: Radioimmunotherapy Agent for Melanoma

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Citações na Scopus
5
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
Título da Revista
ISSN da Revista
Título do Volume
Editora
BENTHAM SCIENCE PUBL LTD
Autores
CAMACHO, Ximena
CALZADA, Victoria
FERNANDEZ, Marcelo
ALONSO, Omar
RIVA, Eloisa
GAMBINI, Juan Pablo
CABRAL, Pablo
Citação
CURRENT RADIOPHARMACEUTICALS, v.10, n.1, p.21-28, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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 degrees C for 18 h. DOTA-Bevacizumab was radiolabeled with (LuCl3)-Lu-177 (15 MBq/mg) at 37 degrees C 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 (LuCl3)-Lu-177 at 37 degrees 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 Lu-177-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 Lu-177-DOTA-Bevacizumab at 24 h. Conclusions: Our results support the potential role of Lu-177-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.
Palavras-chave
VEGF, Bevacizumab, DOTA, Lu-177, radioimmunotherapy agent, melanoma
URI
https://observatorio.fm.usp.br/handle/OPI/21281
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03