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