Evaluation of ((4-Hydroxyphenyl)ethyl)maleimide for Site-Specific Radiobromination of Anti-HER2 Affibody

• 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.

Subject headings

NATURVETENSKAP  -- Kemi -- Organisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Organic Chemistry (hsv//eng)

Keyword

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

Organic chemistry

Organisk kemi

Publication and Content Type

ref (subject category)

art (subject category)