Bevacizumab Radioimmunotherapy (RIT) with Accelerated Blood Clearance Using the Avidin Chase

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.