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