Labeling monoclonal antibodies and F(ab')2 fragments with the alpha-particle-emitting nuclide astatine-211: preservation of immunoreactivity and in vivo localizing capacity.
alpha-Particles such as those emitted by 211At may be advantageous for radioimmunotherapy since they are radiation of high linear energy transfer, depositing high energy over a short distance. Here we describe a strategy for labeling monoclonal antibodies and F(ab')2 fragments with 211At by means of the bifunctional reagent N-succinimidyl 3-(trimethylstannyl)benzoate. An intact antibody, 81C6, and the F(ab')2 fragment of Me1-14 (both reactive with human gliomas) were labeled with 211At in high yield and with a specific activity of up to 4 mCi/mg in a time frame compatible with the 7.2-hr half-life of 211At. Quantitative in vivo binding assays demonstrated that radioastatination was accomplished with maintenance of high specific binding and affinity. Comparison of the biodistribution of 211At-labeled Me1-14 F(ab')2 to that of a nonspecific antibody fragment labeled with 211At and 131I in athymic mice bearing D-54 MG human glioma xenografts demonstrated selective and specific targeting of 211At-labeled antibody in this human tumor model.
Zalutsky
M R
MR
Department of Radiology, Duke University Medical Center, Durham, NC 27710.
Garg
P K
PK
Friedman
H S
HS
Bigner
D D
DD
D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000032:analysis; D001246:Astatine; D002460:Cell Line; D000939:Epitopes / Q000032:analysis; D005910:Glioma / Q000032:analysis; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D008099:Liver / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000032:analysis*; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D011506:Proteins / Q000032:analysis* / Q000276:immunology; D011865:Radioisotope Dilution Technique; D051381:Rats; D019063:Tenascin; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000032:analysis
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D009363:Neoplasm Proteins; D011506:Proteins; D019063:Tenascin; D001246:Astatine