Potential of Three-Step Pretargeting Radioimmunotherapy Using Biotinylated Bevacizumab and Succinylated Streptavidin in Triple-Negative Breast Cancer Xenograft

Background Pretargeting radioimmunotherapy (PRIT) is a promising approach that can reduce long-time retention of blood radioactivity and consequently reduce hematotoxicity. Among the PRIT strategies, the combination of biotin-conjugated mAb and radiolabeled streptavidin (StAv) is a simple and convenient method because of ease of preparation. This study performed three-step (3-step) PRIT using the sequential injection of (1) biotinylated bevacizumab (Bt-BV), (2) avidin, and (3) radiolabeled StAv for the treatment of triple-negative breast cancer (TNBC). Methods Four biodistribution studies were performed using 111 In in tumor-bearing mice to optimize each step of our PRIT methods. Further, a therapeutic study was performed with optimized 3-step PRIT using 90 Y-labeled StAv. Results Based on the biodistribution studies, the protein dose of Bt-BV and avidin was optimized to 100 μg and 10 molar equivalent of BV, respectively. Succinylation of StAv significantly decreased the kidney accumulation level (with succinylation (6.96 ± 0.91) vs without succinylation (20.60 ± 1.47) at 1 h after injection, p < 0.0001) with little effect on tumor accumulation level. In the therapeutic study, tumor growth was significantly suppressed in treatment groups with optimized 3-step PRIT using 90 Y-labeled succinylated StAv compared to that of the no-treatment group ( p < 0.05). Conclusion The 3-step PRIT strategy of this study achieved fast blood clearance and low kidney uptake with little effect on tumor accumulation level, and a certain level of therapeutic effect was consequently observed. These results indicated that the pretargeting treatment of the current study may be effective for human TNBC treatment.