| Order of amino acids in C-terminal cysteine-containing peptide-based chelators influences cellular processing and biodistribution of 99mTc-labeled recombinant Affibody molecules. | |
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MedLine Citation:
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PMID: 21573874 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Affibody molecules constitute a novel class of molecular display selected affinity proteins based on non-immunoglobulin scaffold. Preclinical investigations and pilot clinical data have demonstrated that Affibody molecules provide high contrast imaging of tumor-associated molecular targets shortly after injection. The use of cysteine-containing peptide-based chelators at the C-terminus of recombinant Affibody molecules enabled site-specific labeling with the radionuclide 99mTc. Earlier studies have demonstrated that position, composition and the order of amino acids in peptide-based chelators influence labeling stability, cellular processing and biodistribution of Affibody molecules. To investigate the influence of the amino acid order, a series of anti-HER2 Affibody molecules, containing GSGC, GEGC and GKGC chelators have been prepared and characterized. The affinity to HER2, cellular processing of 99mTc-labeled Affibody molecules and their biodistribution were investigated. These properties were compared with that of the previously studied 99mTc-labeled Affibody molecules containing GGSC, GGEC and GGKC chelators. All variants displayed picomolar affinities to HER2. The substitution of a single amino acid in the chelator had an appreciable influence on the cellular processing of 99mTc. The biodistribution of all 99mTc-labeled Affibody molecules was in general comparable, with the main difference in uptake and retention of radioactivity in excretory organs. The hepatic accumulation of radioactivity was higher for the lysine-containing chelators and the renal retention of 99mTc was significantly affected by the amino acid composition of chelators. The order of amino acids influenced renal uptake of some conjugates at 1 h after injection, but the difference decreased at later time points. Such information can be helpful for the development of other scaffold protein-based imaging and therapeutic radiolabeled conjugates. |
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Authors:
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Mohamed Altai; Helena Wållberg; Anna Orlova; Maria Rosestedt; Seyed Jalal Hosseinimehr; Vladimir Tolmachev; Stefan Ståhl |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-05-15 |
Journal Detail:
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Title: Amino acids Volume: 42 ISSN: 1438-2199 ISO Abbreviation: Amino Acids Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-04-24 Completed Date: 2012-10-01 Revised Date: 2012-10-12 |
Medline Journal Info:
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Nlm Unique ID: 9200312 Medline TA: Amino Acids Country: Austria |
Other Details:
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Languages: eng Pagination: 1975-85 Citation Subset: IM |
Affiliation:
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Division of Biomedical Radiation Sciences, Department of Radiology, Oncology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, 75185, Uppsala, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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chemistry* Animals Chelating Agents / chemistry Cysteine / chemistry* Humans Isotope Labeling Mice Molecular Imaging Peptides / chemical synthesis, chemistry* Receptor, erbB-2 / chemistry* Recombinant Fusion Proteins / chemistry* Technetium / chemistry Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Chelating Agents; 0/Peptides; 0/Recombinant Fusion Proteins; 52-90-4/Cysteine; 7440-26-8/Technetium; EC 2.7.10.1/ERBB2 protein, human; EC 2.7.10.1/Receptor, erbB-2 |
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