Evaluation of ((4-Hydroxyphenyl)ethyl)maleimide for Site-Specific Radiobromination of Anti-HER2 Affibody
2005 (English)In: Bioconjugate chemistry, ISSN 1043-1802, Vol. 16, no 6, 1547-1555 p.Article in journal (Refereed) Published
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 binidng with high affinity to a tumor antigen HER2 was recently developed for radionuclide diagnostics and therapy in vivo. The use of hte positron-emitting nuclide 76Br(T½ = 16.2 h) could imporve the sensitivity of detection of HER2-expressing tumors. A site-specific radiobromination o fa cysteine-containing variant of the anti-HER2 affibody, (ZHER2:4)2-Cys, using ((4-hydroxpyphenyl)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 conjugate to exceed 97%. The label was stable against challenge with large excess of nonlabeled bromide and in a high molar strengt solution. In vitro cell tests demonstraded that radiobrominated affibody binds specifically to the HER2-expressing cel-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.
Place, publisher, year, edition, pages
2005. Vol. 16, no 6, 1547-1555 p.
Animals, Antigens; Neoplasm/analysis/metabolism, Binding Sites, Bromine Radioisotopes/*chemistry, Cell Line; Tumor, Humans, Maleimides/chemistry, Mice, Mice; Nude, Neoplasms; Experimental/pathology, Peptide Library, Peptides/chemistry/*pharmacokinetics, Protein Interaction Mapping, Radiopharmaceuticals/*chemical synthesis/*pharmacokinetics, Receptor; erbB-2/analysis/*metabolism, Research Support; Non-U.S. Gov't, Staphylococcal Protein A/chemistry, Tissue Distribution, Transplantation; Heterologous
IdentifiersURN: urn:nbn:se:uu:diva-74804DOI: 10.1021/bc050056oPubMedID: 16287254OAI: oai:DiVA.org:uu-74804DiVA: diva2:102714