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Tumor Imaging using...
Tumor Imaging using a picomolar affinity HER2 binding affibody molecule
- Artikel/kapitelEngelska2006
Förlag, utgivningsår, omfång ...
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2006-04-17
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American Association for Cancer Research (AACR),2006
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:kth-15608
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-15608URI
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https://doi.org/10.1158/0008-5472.can-05-3521DOI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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QC 20100525
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The detection of cell-bound proteins that are produced due to aberrant gene expression in malignant tumors can provide important diagnostic information influencing patient management. The use of small radiolabeled targeting proteins would enable high-contrast radionuclide imaging of cancers expressing such antigens if adequate binding affinity and specificity could he provided. Here, we describe a HER2-specific 6 kDa Affibody molecule (hereinafter denoted Affibody molecule) with 22 pmol/L affinity that can be used for the visualization of HER2 expression in tumors in vivo using gamma camera. A library for affinity maturation was constructed by re-randomization of relevant positions identified after the alignment of first-generation variants of nanomolar affinity (50 nmol/L). One selected Affibody molecule, Z(HER2:342) showed a > 2,200-fold increase in affinity achieved through a single-library affinity maturation step. When radioiodinated, the affinity-matured Affibody molecule showed clear, high-contrast visualization of HER2-expressing xenografts in mice as early as 6 hours post-injection. The tumor uptake at 4 hours post-injection was improved 4-fold (due to increased affinity) with 9% of the injected dose per gram of tissue in the tumor. Affibody molecules represent a new class of affinity molecules that can provide small sized, high affinity cancer-specific ligands, which may be well suited for tumor imaging.
Ämnesord och genrebeteckningar
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single-chain fv
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antibody fragments
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combinatorial libraries
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directed evolution
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phage display
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proteins
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domain
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cancer
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expression
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ligands
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Magnusson, M.
(författare)
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Eriksson, T. L. J.
(författare)
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Nilsson, M.
(författare)
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Larsson, B.
(författare)
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Hoiden-Guthenherg, I.
(författare)
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Widstrom, C.
(författare)
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Carlsson, J.
(författare)
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Tolmachev, V.
(författare)
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Ståhl, StefanKTH,Molekylär Bioteknologi(Swepub:kth)u1svy8i4
(författare)
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Nilsson, F. Y.
(författare)
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KTHMolekylär Bioteknologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Cancer Research: American Association for Cancer Research (AACR)66:8, s. 4339-43480008-54721538-7445
Internetlänk
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Orlova, A.
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Magnusson, M.
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Eriksson, T. L. ...
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Nilsson, M.
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Larsson, B.
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Hoiden-Guthenher ...
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visa fler...
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Widstrom, C.
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Carlsson, J.
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Tolmachev, V.
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Ståhl, Stefan
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Nilsson, F. Y.
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visa färre...
- Artiklar i publikationen
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Cancer Research
- Av lärosätet
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Kungliga Tekniska Högskolan