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 (90 Y)-labeled biotinylated BV (90 Y-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 (111 In)-BV. The blood clearance enhancement effect of the avidin chase was demonstrated in the normal mouse studies with 111 In-Bt-BV. In the subsequent biodistribution studies with the tumor-bearing mice, an optimized dose of avidin injection subsequent to 111 In-Bt-BV with an appropriate biotin valency successfully accelerated the blood clearance of 111 In-Bt-BV without impairing its tumor accumulation level. The avidin chase enabled an increase in the maximum tolerated dose of 90 Y-Bt-BV to twice as much as that of 90 Y-BV in tumor-bearing mice and thereby significantly improved the therapeutic effect of 90 Y-Bt-BV compared to 90 Y-BV ( p < 0.05). These results underscored the potential usefulness of 90 Y-bevacizumab-RIT with the avidin chase for the treatment of VEGF-positive tumors.