177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma

Author(s): Ximena Camacho, Victoria Calzada, Marcelo Fernandez, Omar Alonso, Roger Chammas, Eloisa Riva, Juan Pablo Gambini, Pablo Cabral.

Journal Name: Current Radiopharmaceuticals

Volume 10 , Issue 1 , 2017

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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.

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Article Details

VOLUME: 10
ISSUE: 1
Year: 2017
Page: [21 - 28]
Pages: 8
DOI: 10.2174/1874471009666161010155246
Price: $58

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