Evaluation of ((4-Hydroxyphenyl)ethyl)maleimide for Site-Specific Radiobromination of Anti-HER2 Affibody
| Autor: | Vladimir Tolmachev, Stefan Sjöberg, Barbro Larsson, Fredrik Nilsson, Ann-Sofie Nilsson, Anna Orlova, Eskender Mume |
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| Rok vydání: | 2005 |
| Předmět: |
Biodistribution
Receptor ErbB-2 Stereochemistry Transplantation Heterologous Biomedical Engineering Mice Nude Pharmaceutical Science Bioengineering Maleimides Mice chemistry.chemical_compound Antigens Neoplasm Peptide Library In vivo Cell Line Tumor Protein Interaction Mapping Animals Humans Tissue Distribution Binding site Staphylococcal Protein A Maleimide Pharmacology Binding Sites Organic Chemistry Neoplasms Experimental In vitro Transplantation chemistry Affibody molecule Bromine Radioisotopes Radiopharmaceuticals Peptides Biotechnology Conjugate |
| Zdroj: | Bioconjugate Chemistry. 16:1547-1555 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/bc050056o |
| Popis: | Affibody molecules are a new class of small phage-display selected proteins using a scaffold domain of the bacterial receptor protein A. They can be selected for specific binding to a large variety of protein targets. An affibody molecule binding with high affinity to a tumor antigen HER2 was recently developed for radionuclide diagnostics and therapy in vivo. The use of the positron-emitting nuclide (76)Br (T(1/2) = 16.2 h) could improve the sensitivity of detection of HER2-expressing tumors. A site-specific radiobromination of a cysteine-containing variant of the anti-HER2 affibody, (Z(HER2:4))(2)-Cys, using ((4-hydroxyphenyl)ethyl)maleimide (HPEM), was evaluated in this study. It was found that HPEM can be radiobrominated with an efficiency of 83 +/- 0.4% and thereafter coupled to freshly reduced affibody with a yield of 65.3 +/- 3.9%. A "one-pot" labeling enabled the radiochemical purity of the conjugate to exceed 97%. The label was stable against challenge with large excess of nonlabeled bromide and in a high molar strength solution. In vitro cell tests demonstrated that radiobrominated affibody binds specifically to the HER2-expressing cell-line, SK-OV-3. Biodistribution studies in nude mice bearing SK-OV-3 xenografts have shown tumor accumulation of 4.8 +/- 2.2% IA/g and good tumor-to-normal tissue ratios. |
| Databáze: | OpenAIRE |
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