Bevacizumab Radioimmunotherapy (RIT) with Accelerated Blood Clearance Using the Avidin Chase.
Mol Pharm
; 15(6): 2165-2173, 2018 06 04.
Article
en En
| MEDLINE
| ID: mdl-29733658
The overexpression of vascular endothelial growth factor (VEGF) in varying types of solid tumor renders radioimmunotherapy (RIT) with the anti-VEGF antibody bevacizumab (BV) a promising treatment. However, the slow blood clearance of BV, which may increase the occurrence risk of hematotoxicity, hinders the application of BV-RIT. Using the avidin chase is a long-known blood clearance enhancement strategy for biotinylated-mAb. To enhance RIT efficacy by increasing the radioactivity dose, we evaluated the ability of avidin to accelerate the blood clearance of yttrium-90 (90Y)-labeled biotinylated BV (90Y-Bt-BV) in a xenograft mouse model of triple-negative breast cancer (TNBC). The biodistribution study in the TNBC xenograft mice confirmed the high and specific tumor accumulation of the indium-111 (111In)-BV. The blood clearance enhancement effect of the avidin chase was demonstrated in the normal mouse studies with 111In-Bt-BV. In the subsequent biodistribution studies with the tumor-bearing mice, an optimized dose of avidin injection subsequent to 111In-Bt-BV with an appropriate biotin valency successfully accelerated the blood clearance of 111In-Bt-BV without impairing its tumor accumulation level. The avidin chase enabled an increase in the maximum tolerated dose of 90Y-Bt-BV to twice as much as that of 90Y-BV in tumor-bearing mice and thereby significantly improved the therapeutic effect of 90Y-Bt-BV compared to 90Y-BV ( p < 0.05). These results underscored the potential usefulness of 90Y-bevacizumab-RIT with the avidin chase for the treatment of VEGF-positive tumors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Radioisótopos de Itrio
/
Avidina
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Radioinmunoterapia
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Inmunoconjugados
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Neoplasias de la Mama Triple Negativas
/
Bevacizumab
Tipo de estudio:
Evaluation_studies
/
Prognostic_studies
Límite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
Mol Pharm
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACIA
/
FARMACOLOGIA
Año:
2018
Tipo del documento:
Article
Pais de publicación:
Estados Unidos