Preparation and evaluation of 211At labelled antineoplastic antibodies.
OBJECTIVE
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.
Walte
Almut
A
Klinik für Nuklearmedizin, Medizinische Hochschule Hannover, Hannover, Germany.
Sriyapureddy
Siva Sankar Reddy
SS
Korkmaz
Zekiye
Z
Krull
Doris
D
Bolte
Oliver
O
Hofmann
Michael
M
Meyer
Geerd-J
GJ
Knapp
Wolfram H
WH
D000617:Aminoglycosides / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D001246:Astatine; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D000939:Epitopes; D000079982:Gemtuzumab; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D016499:Radioimmunotherapy / Q000379:methods*; D000069283:Rituximab
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000939:Epitopes; D000069283:Rituximab; D000079982:Gemtuzumab; D001246:Astatine