Labeling monoclonal antibodies and F(ab')2 fragments with the alpha-particle-emitting nuclide astatine-211: preservation of immunoreactivity and in vivo localizing capacity.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Zalutsky, MR; Garg, PK; Friedman, HS; Bigner, DD
Published Date
- September 1989
Published In
Volume / Issue
- 86 / 18
Start / End Page
- 7149 - 7153
PubMed ID
- 2476813
Pubmed Central ID
- PMC298013
International Standard Serial Number (ISSN)
- 0027-8424
Digital Object Identifier (DOI)
- 10.1073/pnas.86.18.7149
Language
- eng
Conference Location
- United States