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  • Altai, MohamedUppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev (author)

Preclinical evaluation of anti-HER2 Affibody molecules site-specifically labeled with In-111 using a maleimido derivative of NODAGA

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • Elsevier BV,2012
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:kth-96444
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-96444URI
  • https://doi.org/10.1016/j.nucmedbio.2011.10.013DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-164424URI

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  • Language:English
  • Summary in:English

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

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  • QC 20120605
  • Introduction: Affibody molecules have demonstrated potential for radionuclide molecular imaging. The aim of this study was to synthesize and evaluate a maleimido derivative of the 1,4,7-triazacyclononane-l-glutaric acid-4,7-diacetic acid (NODAGA) for site-specific labeling of anti-HER2 Affibody molecule. Methods: The maleimidoethylmonoamide NODAGA (MMA-NODAGA) was synthesized and conjugated to Z(HER2:2395) Affibody molecule having a C-terminal cysteine. Labeling efficiency, binding specificity to and cell internalization by HER2-expressing cells of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) were studied. Biodistribution of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) was compared in mice. Results: The affinity of [MMA-NODAGA-Cys(61)]-Z(HER2:2395) binding to HER2 was 67 pM. The In-1111-labeling yield was 99.6%+/- 0.5% after 30 min at 60 degrees C. [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) bound specifically to HER2-expressing cells in vitro and in vivo. Tumor uptake of [In-111-MMA-NODAGA-Cys(61)]-ZHER(2:2395) in mice bearing DU-145 xenografts (4.7%+/- 0.8% ID/g) was lower than uptake of [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) (7.5%+/- 1.6% ID/g). However, tumor-to-organ ratios were higher for [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) due to higher clearance rate from normal tissues. Conclusions: MMA-NODAGA is a promising chelator for site-specific labeling of targeting proteins containing unpaired cysteine. Appreciable influence of chelators on targeting properties of Affibody molecules was demonstrated.

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  • Perols, AnnaKTH,Molekylär Bioteknologi(Swepub:kth)u11lpgnl (author)
  • Eriksson Karlström, AmelieKTH,Molekylär Bioteknologi(Swepub:kth)u10x6l4n (author)
  • Sandström, MattiasUppsala universitet,Avdelningen för sjukhusfysik(Swepub:uu)masan637 (author)
  • Boschetti, Frederic (author)
  • Orlova, AnnaUppsala universitet,Plattformen för preklinisk PET,Anna Orlova(Swepub:uu)annaorlo (author)
  • Tolmachev, VladimirUppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev(Swepub:uu)vladtolm (author)
  • Uppsala universitetEnheten för biomedicinsk strålningsvetenskap (creator_code:org_t)

Related titles

  • In:Nuclear Medicine and Biology: Elsevier BV39:4, s. 518-5290969-80511872-9614

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