Potential of three-step pretargeting radioimmunotherapy using biotinylated bevacizumab and succinylated streptavidin in triple-negative breast cancer xenograft.

Abstract

OBJECTIVE:

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 its 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 111In in tumor-bearing mice to optimize each step of our PRIT methods. Further, a therapeutic study was performed with optimized 3-step PRIT using 90Y-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 the tumor accumulation level. In the therapeutic study, tumor growth was significantly suppressed in treatment groups with optimized 3-step PRIT using 90Y-labeled succinylated StAv compared to that of the no-treatment group (p < 0.05).

CONCLUSIONS:

The 3-step PRIT strategy of this study achieved fast blood clearance and low kidney uptake with little effect on the tumor accumulation level, and a certain degree of therapeutic effect was consequently observed. These results indicated that the pretargeting treatment of the current study may be effective for human TNBC treatment.

• Authors: Wenchao Gu, Ryan Yudistiro, Hirofumi Hanaoka, Natsumi Katsumata, Yoshito Tsushima
• Journal: Annals of nuclear medicine (Ann Nucl Med) Vol. 35 Issue 4 Pg. 514-522 (Apr 2021) ISSN: 1864-6433 [Electronic] Japan
• PMID: 33582981 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Immunological
• Immunoconjugates
• Indium Radioisotopes
• Succinimides
• Indium
• Bevacizumab
• indium trichloride
• Biotin
• Streptavidin
• Indium-111
• N-hydroxysuccinimide

Topics

• Animals
• Antineoplastic Agents, Immunological (chemistry, pharmacokinetics)
• Bevacizumab (chemistry, pharmacokinetics)
• Biotin (chemistry)
• Dose-Response Relationship, Immunologic
• Female
• Heterografts
• Immunoconjugates (therapeutic use)
• Indium (chemistry)
• Indium Radioisotopes (chemistry)
• Kidney
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Radioimmunotherapy
• Streptavidin (chemistry, pharmacokinetics)
• Succinimides (chemistry)
• Triple Negative Breast Neoplasms (drug therapy)