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  • Tran, ThuyUppsala universitet,Enheten för biomedicinsk strålningsvetenskap (author)

99mTc-maEEE-ZHER2:342, an Affibody Molecule-Based Tracer for the Detection of HER2 Expression in Malignant Tumors

  • Article/chapterEnglish2007

Publisher, publication year, extent ...

  • 2007-10-19
  • American Chemical Society (ACS),2007
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-9723
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-9723URI
  • https://doi.org/10.1021/bc7002617DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-17053URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20100716
  • Detection of HER2-overexpression in tumors and metastases is important for the selection of patients who will benefit from trastuzumab treatment. Earlier investigations showed successful imaging of HER2-positive tumors in patients using indium- or gallium-labeled Affibody molecules. The goal of this study was to evaluate the use of 99mTc-labeled Affibody molecules for the detection of HER2 expression. The Affibody molecule ZHER2:342 with the chelator sequences mercaptoacetyl-Gly-Glu-Gly (maGEG) and mercaptoacetyl-Glu-Glu-Glu (maEEE) was synthesized by peptide synthesis and labeled with technetium-99m. Binding specificity, cellular retention, and in vitro stability were investigated. The biodistribution of 99mTc-maGEG-ZHER2:342 and 99mTc-maEEE-ZHER2:342 was compared with 99mTc-maGGG-ZHER2:342 in normal mice, and the tumor targeting properties of 99mTc-maEEE-ZHER2:342 were determined in SKOV-3 xenografted nude mice. The results showed that the Affibody molecules were efficiently labeled with technetium-99m. The labeled conjugates were highly stable in vitro with preserved HER2-binding capacity. The use of glutamic acid in the chelator sequences for 99mTc-labeling of ZHER2:342 reduced the hepatobiliary excretion 3-fold with a single Gly-to-Glu substitution and 10-fold with three Gly-to-Glu substitutions. 99mTc-maEEE-ZHER2:342 showed a receptor-specific tumor uptake of 7.9 ± 1.0 %IA/g and a tumor-to-blood ratio of 38 at 4 h pi. Gamma-camera imaging with 99mTc-maEEE-ZHER2:342 could detect HER2-expressing tumors in xenografts already at 1 h pi. It was concluded that peptide synthesis for the coupling of chelator sequences to Affibody molecules for 99mTc labeling is an efficient way to modify the in vivo kinetics. Increased hydrophilicity, combined with improved stability of the mercaptoacetyl-triglutamyl chelator, resulted in favorable biodistribution, making 99mTc-maEEE-ZHER2:342 a promising tracer for clinical imaging of HER2 overexpression in tumors.

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  • Engfeldt, TorunKTH,Molekylär Bioteknologi,School of Biotechnology, Royal Institute of Technology, Stockholm, Sweden(Swepub:kth)u18tluq7 (author)
  • Orlova, AnnaUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi(Swepub:uu)annaorlo (author)
  • Sandström, MattiasUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi (author)
  • Feldwisch, JoachimUppsala universitet,Enheten för biomedicinsk strålningsvetenskap(Swepub:uu)joafe691 (author)
  • Abrahmsén, LarsAffibody AB, Bromma (author)
  • Wennborg, AndersAffibody AB, Bromma (author)
  • Tolmachev, VladimirUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,Institutionen för medicinska vetenskaper(Swepub:uu)vladtolm (author)
  • Eriksson Karlström, AmelieKTH,Molekylär Bioteknologi,School of Biotechnology, Royal Institute of Technology, Stockholm, Sweden(Swepub:kth)u10x6l4n (author)
  • Uppsala universitetEnheten för biomedicinsk strålningsvetenskap (creator_code:org_t)

Related titles

  • In:Bioconjugate chemistry: American Chemical Society (ACS)18:6, s. 1956-19641043-18021520-4812

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