AvidinOX for highly efficient tissue-pretargeted radionuclide therapy.

ABSTRACT

Avidin is widely used in vitro for its capacity to bind biotin. However, avidin's in vivo use is limited by its short residence in blood and tissues. An avidin variant, named AvidinOX, has been recently described. This product is obtained by 4-hydroxyazobenzene-2'-carboxylic acid-assisted sodium periodate oxidation of avidin. This method generates aldehyde groups from avidin carbohydrates, sparing biotin-binding sites from inactivation. AvidinOX binds cellular and interstitial protein amino groups through Schiff's bases, resulting in a tissue half-life of 2 weeks, compared with 2 hours of native avidin. Binding of AvidinOX occurs in normal and neoplastic tissues. Data show that AvidinOX, administered intranipple in the breast of transgenic BALB/neuT mice, is highly efficient for capturing (90)Y-biotinDOTA, intravenously injected after 48 hours, leading to eradication of multifocal cancer lesions. Efficacy data, together with good tolerability results, indicate that AvidinOX is a highly innovative reagent for tissue-pretargeted radionuclide therapy.