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177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma

[ Vol. 10 , Issue. 1 ]

Author(s):

Ximena Camacho, Victoria Calzada, Marcelo Fernandez, Omar Alonso, Roger Chammas, Eloisa Riva, Juan Pablo Gambini and Pablo Cabral   Pages 21 - 28 ( 8 )

Abstract:


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.

Keywords:

VEGF, Bevacizumab, DOTA, 177Lu, radioimmunotherapy agent, melanoma.

Affiliation:

Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo, Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo, Centro de Medicina Nuclear, Hospital de Clínicas , Laboratório de Oncologia Experimental, Faculdade de Medicina, Universidade de Sao Paulo, Av. Dr. Arnaldo Nº 455- Cerqueira Cesar - CEP: 01246903 , Sao Paulo, Clínica Hematológica. Hospital de Clínicas. Facultad de Medicina. Universidad de la Republica, Montevideo, Centro de Medicina Nuclear, Hospital de Clínicas , Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo

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