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Targeting of HER2-e...
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Ahlgren, SaraUppsala universitet,Institutionen för medicinska vetenskaper
(författare)
Targeting of HER2-expressing tumors with a site-specifically 99mTc-labeled recombinant affibody molecule, ZHER2:2395, with C-terminally engineered cysteine
- Artikel/kapitelEngelska2009
Förlag, utgivningsår, omfång ...
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2009-04-16
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Society of Nuclear Medicine,2009
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-122172
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-122172URI
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https://doi.org/10.2967/jnumed.108.056929DOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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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.
Ämnesord och genrebeteckningar
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Affibody molecule
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technetium
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imaging
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HER2
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C-terminal cysteine
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MEDICINE
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MEDICIN
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Wållberg, HelenaUppsala universitet,Enheten för biomedicinsk strålningsvetenskap,BMS
(författare)
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Tran, Thuy A.Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,BMS
(författare)
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Widström, CharlesUppsala universitet,Avdelningen för sjukhusfysik
(författare)
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Hjertman, MagnusAffibody AB, Stockholm, Sweden
(författare)
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Abrahmsén, LarsAffibody AB, Stockholm, Sweden
(författare)
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Berndorff, DietmarGlobal Drug Discovery, Bayer Schering Pharma AG, Berlin, Germany
(författare)
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Dinkelborg, Ludger M.Global Drug Discovery, Bayer Schering Pharma AG, Berlin, Germany
(författare)
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Cyr, John E.Global Drug Discovery, Bayer Schering Pharma AG, Berlin, Germany
(författare)
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Feldwisch, JoachimUppsala universitet,Enheten för biomedicinsk strålningsvetenskap,BMS(Swepub:uu)joafe691
(författare)
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Orlova, AnnaUppsala universitet,Enheten för biomedicinsk strålningsvetenskap,BMS(Swepub:uu)annaorlo
(författare)
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Tolmachev, VladimirUppsala universitet,Enheten för biomedicinsk strålningsvetenskap,BMS(Swepub:uu)vladtolm
(författare)
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Uppsala universitetInstitutionen för medicinska vetenskaper
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Nuclear Medicine: Society of Nuclear Medicine50:5, s. 781-7890161-55051535-56672159-662X
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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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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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