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Labelling chemistry...
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Fortin, Marc-AndréUppsala universitet,Enheten för biomedicinsk strålningsvetenskap
(author)
Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma
- Article/chapterEnglish2007
Publisher, publication year, extent ...
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-104537
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-104537URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The direct instillation of radiolabelled conjugates in the urinary bladder is a promising path for the treatment of bladder carcinoma. The targeting of HER2/neu receptors expressed on the surface of many bladder carcinoma cells shows potential to be developed as a therapeutic strategy, and patients identified with a high risk of progression may benefit from adjuvant targeted radionuclide therapy. A phage-display selected Affibody molecule (Z(HER2:342)) which binds to HER2/neu with picomolar affinity, can be used for targeting HER2/neu-expressing bladder carcinomas. A DOTA-derivative of Z(HER2:342), designated as DOTA-Z(HER2:342)-3, is considered as a suitable targeting agent for therapy. The DOTA chelator provides stable labelling with radiometals, and the low molecular weight (7.2 kDa) of the DOTA-Z(HER2:342)-3 compound is expected to enable efficient tumor penetration. DOTA-Z(HER2:342)-3 was radiolabelled with 90Y and 177Lu in 1 M ammonium acetate buffer, at pH 5.5, and in the presence of ascorbic acid. Nearly quantitative labelling yields were achieved for both nuclides after 15 min of incubation at 60 degrees C. After chelation, the conjugates retained their capacity to specifically bind to HER2/neu-expressing SKOV-3 cells. The radiolabelled affibody conjugate (DOTA-Z(HER2:342)-3) demonstrated high antigen-binding capacity and good cellular retention. Biodistribution in normal mice demonstrated low uptake in all organs and tissues except for kidneys.
Subject headings and genre
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Animals
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Cell Line; Tumor
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Cell Survival/drug effects
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Humans
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Mice
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Recombinant Fusion Proteins/pharmacokinetics/*therapeutic use
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Urinary Bladder Neoplasms/*drug therapy/pathology
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Yttrium Radioisotopes/pharmacokinetics/*therapeutic use
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MEDICINE
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MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
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Orlova, AnnaUppsala universitet,Enheten för biomedicinsk strålningsvetenskap(Swepub:uu)annaorlo
(author)
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Malmström, Per-UnoUppsala universitet,Urologkirurgi(Swepub:uu)perunoms
(author)
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Tolmachev, VladimirUppsala universitet,Enheten för biomedicinsk strålningsvetenskap(Swepub:uu)vladtolm
(author)
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Uppsala universitetEnheten för biomedicinsk strålningsvetenskap
(creator_code:org_t)
Related titles
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In:International Journal of Molecular Medicine19:2, s. 285-2911107-37561791-244X
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