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Design, synthesis a...
Design, synthesis and biological evaluation of a multifunctional HER2-specific Affibody molecule for molecular imaging
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- Tran, Thuy A., 1980- (author)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Rosik, Daniel (author)
- KTH,Molekylär Bioteknologi,Affibody AB, Bromma
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- Abrahmsén, Lars (author)
- Affibody AB, Bromma
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- Sandström, Mattias (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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- Sjöberg, Anna (author)
- Affibody AB, Bromma
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- Wållberg, Helena (author)
- KTH,Molekylär Bioteknologi,School of Biotechnology, Division of Molecular Biotechnology, Royal Institute of Technology, Stockholm, Sweden
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- Ahlgren, Sara (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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- Orlova, Anna (author)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Institutionen för medicinska vetenskaper
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(creator_code:org_t)
- 2009-06-06
- 2009
- English.
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In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 36:11, s. 1864-1873
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Purpose: The purpose of this study was to design and evaluate a novel platform for labelling of Affibody molecules, enabling for both recombinant and synthetic production and for site-specific labelling with 99mTc or trivalent radiometals. Methods: The HER2-specific Affibody molecule PEP05352 was made by peptide synthesis. The chelator sequence SECG (serine-glutamic acid-cysteine-glycine) was anchored on the C-terminal to allow 99mTc-labelling. The cysteine can alternatively serve as a conjugation site of the chelator DOTA for indium-labelling. The resulting 99mTc- and 111In-labelled Affibody molecules were evaluated both in vitro and in vivo. Results: Both conjugates retained their capacity to bind to HER2 receptors in vitro and in vivo. The tumour-to-blood ratio in LS174T xenografts was 30 at 4 h p.i. for both conjugates. Biodistribution data showed that 99mTc-labelled Affibody molecule had 4-fold lower kidney accumulation compared with 111In-labelled Affibody molecule while the accumulation in other organs was similar. Gamma-camera imaging of the conjugates could clearly visualise the tumours 4 h after injection. Conclusions: Incorporation of C-terminal SECG sequence in Affibody molecules provides a general multifunctional platform for site-specific labelling with different nuclides (technetium, indium, gallium, cobalt, or yttrium) and for a flexible production (chemical synthesis or recombinant).
Subject headings
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology (hsv//eng)
Keyword
- HER2
- Affibody molecules
- peptide synthesis
- imaging
- chelator
- technetium
- indium
- SPECT
- MEDICINE
- MEDICIN
- Biomedical Radiation Science
- Biomedicinsk strålningsvetenskap
- Bioengineering
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Tran, Thuy A., 1 ...
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Rosik, Daniel
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Abrahmsén, Lars
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Sandström, Matti ...
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Sjöberg, Anna
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Wållberg, Helena
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show more...
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Ahlgren, Sara
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Orlova, Anna
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Tolmachev, Vladi ...
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- About the subject
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- ENGINEERING AND TECHNOLOGY
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ENGINEERING AND ...
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and Industrial Biote ...
- Articles in the publication
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European Journal ...
- By the university
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Uppsala University
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Royal Institute of Technology