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Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
09:44

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Published on: January 29, 2019

AvidinOX for highly efficient tissue-pretargeted radionuclide therapy.

Rita De Santis1, Barbara Leoni, Antonio Rosi

  • 1Department of Immunology, Sigma-Tau SpA R&D, Rome, Italy. rita.desantis@sigma-tau.it

Cancer Biotherapy & Radiopharmaceuticals
|April 29, 2010
PubMed
Summary

AvidinOX, a modified avidin, shows prolonged tissue retention for enhanced radionuclide therapy. This innovative reagent effectively targets and eradicates cancer lesions with good tolerability.

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Area of Science:

  • Biochemistry
  • Bioconjugation Chemistry
  • Oncology

Background:

  • Native avidin has limited in vivo application due to its short biological half-life.
  • Avidin's biotin-binding capacity is crucial for in vitro applications.
  • Developing avidin variants with improved pharmacokinetic properties is essential for in vivo applications.

Purpose of the Study:

  • To describe the generation and characterization of AvidinOX, a novel avidin variant.
  • To evaluate the in vivo tissue retention and binding properties of AvidinOX.
  • To assess the efficacy of AvidinOX in a preclinical model of breast cancer for radionuclide therapy.

Main Methods:

  • AvidinOX was produced via sodium periodate oxidation of avidin, facilitated by 4-hydroxyazobenzene-2'-carboxylic acid.
  • Aldehyde groups were introduced onto avidin carbohydrates, preserving biotin-binding sites.
  • AvidinOX tissue retention and binding were assessed, followed by evaluation in a transgenic mouse model for pretargeted radionuclide therapy using (90)Y-biotinDOTA.

Main Results:

  • AvidinOX demonstrated a significantly extended tissue half-life of 2 weeks compared to native avidin's 2 hours.
  • AvidinOX effectively binds to cellular and interstitial protein amino groups via Schiff's base formation in both normal and neoplastic tissues.
  • Intraniuple administration of AvidinOX in BALB/neuT mice resulted in efficient capture of (90)Y-biotinDOTA, leading to the eradication of multifocal breast cancer lesions.

Conclusions:

  • AvidinOX exhibits excellent tissue retention and specific binding, overcoming the limitations of native avidin for in vivo applications.
  • AvidinOX facilitates highly efficient pretargeted radionuclide therapy, as demonstrated by the successful eradication of breast cancer lesions in a preclinical model.
  • AvidinOX represents a promising and innovative reagent for tissue-pretargeted radionuclide therapy with demonstrated efficacy and good tolerability.