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Evaluation of ((4-H...
Evaluation of ((4-Hydroxyphenyl)ethyl)maleimide for Site-Specific Radiobromination of Anti-HER2 Affibody
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- Mume, Eskender (författare)
- Uppsala universitet,Kemiska institutionen,Organisk kemi II
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- Orlova, Anna (författare)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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Larsson, Barbro (författare)
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Nilsson, Ann-Sofie (författare)
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- Nilsson, Fredrik Y. (författare)
- Uppsala universitet,Organisk kemi II
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- Sjöberg, Stefan (författare)
- Uppsala universitet,Kemiska institutionen,Organisk kemi II
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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(creator_code:org_t)
- 2005-10-27
- 2005
- Engelska.
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Ingår i: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 16:6, s. 1547-1555
- Relaterad länk:
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Nyckelord
- 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
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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