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Order of amino acid...
Order of amino acids in C-terminal cysteine-containing peptide-based chelators influences cellular processing and biodistribution of Tc-99m-labeled recombinant Affibody molecules
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- Altai, Mohamed (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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- Wållberg, Helena (författare)
- KTH,Molekylär Bioteknologi
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- Orlova, Anna (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Anna Orlova
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- Rosestedt, Maria (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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- Hosseinimehr, Seyed Jalal (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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- Ståhl, Stefan (författare)
- KTH,Molekylär Bioteknologi
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(creator_code:org_t)
- 2011-05-15
- 2012
- Engelska.
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Ingår i: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 42:5, s. 1975-1985
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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 Tc-99m. 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 Tc-99m-labeled Affibody molecules and their biodistribution were investigated. These properties were compared with that of the previously studied Tc-99m-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 Tc-99m. The biodistribution of all Tc-99m-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 Tc-99m 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Affibody molecule
- Technetium-99m
- Molecular imaging
- HER2
- C-terminal cysteine
- Peptide-based chelator
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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