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Imaging of HER2-exp...
Imaging of HER2-expressing tumours using a synthetic Affibody molecule containing the 99mTc-chelating mercaptoacetyl-glycyl-glycyl-glycyl (MAG3) sequence
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- Engfeldt, Torun (författare)
- KTH,Molekylär Bioteknologi
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- Orlova, Anna (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University
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- Tran, Thuy (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University
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- Bruskin, Alexander (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University
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- Widström, Charles (författare)
- Department of Hospital Physics, Uppsala University Hospital
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- Eriksson Karlström, Amelie (författare)
- KTH,Molekylär Bioteknologi
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University
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(creator_code:org_t)
- 2006-12-05
- 2007
- Engelska.
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 34:5, s. 722-733
- 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
- PURPOSE: Expression of human epidermal growth factor receptor type 2 (HER2) in malignant tumours possesses well-documented prognostic and predictive value. Non-invasive imaging of expression can provide valuable diagnostic information, thereby influencing patient management. Previously, we reported a phage display selection of a small (about 7 kDa) protein, the Affibody molecule Z(HER2:342), which binds HER2 with subnanomolar affinity, and demonstrated the feasibility of targeting of HER2-expressing xenografts using radioiodinated Z(HER2:342). The goal of this study was to develop a method for (99m)Tc labelling of Z(HER2:342) using the MAG3 chelator, which was incorporated into Z(HER2:342) using peptide synthesis, and evaluate the targeting properties of the labelled conjugate. METHODS: MAG3-Z(HER2:342) was assembled using Fmoc/tBu solid phase peptide synthesis. Biochemical characterisation of the agent was performed using RP-HPLC, ESI-MS, biosensor studies and circular dichroism. A procedure for (99m)Tc labelling in the presence of sodium/potassium tartrate was established. Tumour targeting was evaluated by biodistribution study and gamma camera imaging in xenograft-bearing mice. Biodistribution of (99m)Tc-MAG3-Z(HER2:342) and (125)I-para-iodobenzoate -Z(HER2:342) was compared 6 h p.i. RESULTS: Synthetic MAG3-Z(HER2:342) possessed an affinity of 0.2 nM for HER2 receptors. The peptide was labelled with (99m)Tc with an efficiency of about 75-80%. Labelled (99m)Tc-MAG3-Z(HER2:342) retained capacity to bind specifically HER2-expressing SKOV-3 cells in vitro. (99m)Tc-MAG3-Z(HER2:342) showed specific tumour targeting with a contrast similar to a radioiodinated analogue in mice bearing LS174T xenografts. Gamma camera imaging demonstrated clear and specific visualisation of HER2 expression. CONCLUSION: Incorporation of a mercaptoacetyl-containing chelating sequence during chemical synthesis enabled site-specific (99m)Tc labelling of the Z(HER2:342) Affibody molecule with preserved targeting capacity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
Nyckelord
- Biodistribution
- HER2
- Peptide
- Targeting
- Technetium-99m
- MEDICINE
- MEDICIN
- Radiological research
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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