Preparation and evaluation of 211At labelled antineoplastic antibodies

J Pharm Pharm Sci. 2007;10(2):277s-285s.

Abstract

Purpose: The objective of this study was to determine and verify the stability of 211At-labelled antibodies under physiological conditions and their specific cell-binding capacity for selected epitopes, in order to evaluate the potential of 211At for alpha-radioimmunotherapy.

Methods: 211At was produced at the department's cyclotron and was linked via the intermediate 3-211At-succinimidyl-benzoate (SAB) to the antineoplastic antibodies rituximab, gemtuzumab and gemtuzumab ozogamicin. The stability of the labelled antibodies was determined in serum for 21 h. Cell-binding experiments on HL-60 and CI-1 cells included kinetic, saturation and competitive binding studies. For comparison the binding to antigen-negative cells was determined. The binding specificity and affinity and the IC50-values were evaluated.

Results: A consistent yield of 30% and a specific activity of 3 MBq/nmol was obtained. The stability of 211At-antibodies in murine serum exceeded 85% at 37 degrees C. Cell-binding to antigen-positive cells was >25%, while binding to antigen-negative cells did not exceed the unspecific binding and was smaller than 1%. IC50 values ranged between 2 and 11 nmol/L.

Conclusions: A routine preparation of 211At-labelled antibodies was established and the stability of the 211At-labelled antibodies under physiologic conditions was verified. Apparently, labelling of antibodies with 211At by the method described does not compromise the affinity and specificity to the respective epitopes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / administration & dosage
  • Aminoglycosides / chemistry
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Astatine*
  • Binding, Competitive
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Stability
  • Epitopes
  • Gemtuzumab
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Radioimmunotherapy / methods*
  • Rituximab

Substances

  • Aminoglycosides
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Epitopes
  • Rituximab
  • Gemtuzumab
  • Astatine