Document Detail

Order of amino acids in C-terminal cysteine-containing peptide-based chelators influences cellular processing and biodistribution of 99mTc-labeled recombinant Affibody molecules.
MedLine Citation:
PMID:  21573874     Owner:  NLM     Status:  MEDLINE    
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.
Mohamed Altai; Helena Wållberg; Anna Orlova; Maria Rosestedt; Seyed Jalal Hosseinimehr; Vladimir Tolmachev; Stefan Ståhl
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-05-15
Journal Detail:
Title:  Amino acids     Volume:  42     ISSN:  1438-2199     ISO Abbreviation:  Amino Acids     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-24     Completed Date:  2012-10-01     Revised Date:  2012-10-12    
Medline Journal Info:
Nlm Unique ID:  9200312     Medline TA:  Amino Acids     Country:  Austria    
Other Details:
Languages:  eng     Pagination:  1975-85     Citation Subset:  IM    
Division of Biomedical Radiation Sciences, Department of Radiology, Oncology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, 75185, Uppsala, Sweden.
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MeSH Terms
Amino Acids / chemistry*
Chelating Agents / chemistry
Cysteine / chemistry*
Isotope Labeling
Molecular Imaging
Peptides / chemical synthesis,  chemistry*
Receptor, erbB-2 / chemistry*
Recombinant Fusion Proteins / chemistry*
Technetium / chemistry
Tissue Distribution
Reg. No./Substance:
0/Amino Acids; 0/Chelating Agents; 0/Peptides; 0/Recombinant Fusion Proteins; 52-90-4/Cysteine; 7440-26-8/Technetium; EC protein, human; EC, erbB-2

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