Preparation and evaluation of 211At labelled antineoplastic antibodies.

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.