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Targeting of HER2-e...
Targeting of HER2-expressing tumors with a site-specifically 99mTc-labeled recombinant affibody molecule, ZHER2:2395, with C-terminally engineered cysteine
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- Ahlgren, Sara (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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- Wållberg, Helena (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,BMS
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- Tran, Thuy A. (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,BMS
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- Widström, Charles (författare)
- Uppsala universitet,Avdelningen för sjukhusfysik
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- Hjertman, Magnus (författare)
- Affibody AB, Stockholm, Sweden
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- Abrahmsén, Lars (författare)
- Affibody AB, Stockholm, Sweden
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- Berndorff, Dietmar (författare)
- Global Drug Discovery, Bayer Schering Pharma AG, Berlin, Germany
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- Dinkelborg, Ludger M. (författare)
- Global Drug Discovery, Bayer Schering Pharma AG, Berlin, Germany
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- Cyr, John E. (författare)
- Global Drug Discovery, Bayer Schering Pharma AG, Berlin, Germany
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- Feldwisch, Joachim (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,BMS
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- Orlova, Anna (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,BMS
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,BMS
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(creator_code:org_t)
- 2009-04-16
- 2009
- Engelska.
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 50:5, s. 781-789
- Relaterad länk:
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http://jnm.snmjourna...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- The detection of human epidermal growth factor receptor type 2 (HER2) expression in malignant tumors provides important information influencing patient management. Radionuclide in vivo imaging of HER2 may permit the detection of HER2 in both primary tumors and metastases by a single noninvasive procedure. Small (7 kDa) high-affinity anti-HER2 Affibody molecules may be suitable tracers for SPECT visualization of HER2-expressing tumors. The use of generator-produced (99m)Tc as a label would facilitate the prompt translation of anti-HER2 Affibody molecules into use in clinics. METHODS: A C-terminal cysteine was introduced into the Affibody molecule Z(HER2:342) to enable site-specific labeling with (99m)Tc. Two recombinant variants, His(6)-Z(HER2:342)-Cys (dissociation constant [K(D)], 29 pM) and Z(HER2:2395)-Cys, lacking a His tag (K(D), 27 pM), were labeled with (99m)Tc in yields exceeding 90%. The binding specificity and the cellular processing of Affibody molecules were studied in vitro. Biodistribution and gamma-camera imaging studies were performed in mice bearing HER2-expressing xenografts. RESULTS: (99m)Tc-His(6)-Z(HER2:342)-Cys was capable of targeting HER2-expressing SKOV-3 xenografts in SCID mice, but the liver radioactivity uptake was high. A series of comparative biodistribution experiments indicated that the presence of the His tag caused elevated accumulation in the liver. (99m)Tc-Z(HER2:2395)-Cys, not containing a His tag, showed low uptake in the liver and high and specific uptake in HER2-expressing xenografts. Four hours after injection, the radioactivity uptake values (percentage of injected activity per gram of tissue [%IA/g]) were 6.9 +/- 2.5 (mean +/- SD) %IA/g in LS174T xenografts (moderate level of HER2 expression) and 15 +/- 3 %IA/g in SKOV-3 xenografts (high level of HER2 expression). The corresponding tumor-to-blood ratios were 88 +/- 24 and 121 +/- 24, respectively. Both LS174T and SKOV-3 xenografts were clearly visualized with a clinical gamma-camera 1 h after injection of (99m)Tc-Z(HER2:2395)-Cys. CONCLUSION: The Affibody molecule (99m)Tc-Z(HER2:2395)-Cys is a promising tracer for SPECT visualization of HER2-expressing tumors.
Nyckelord
- Affibody molecule
- technetium
- imaging
- HER2
- C-terminal cysteine
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
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Ahlgren, Sara
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Wållberg, Helena
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Tran, Thuy A.
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Widström, Charle ...
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Hjertman, Magnus
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Abrahmsén, Lars
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visa fler...
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Berndorff, Dietm ...
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Dinkelborg, Ludg ...
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Cyr, John E.
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Feldwisch, Joach ...
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Orlova, Anna
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Tolmachev, Vladi ...
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Journal of Nucle ...
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Uppsala universitet