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  • Ekblad, TorunKTH,Skolan för bioteknologi (BIO) (author)

Development and preclinical characterisation of 99mTc-labelled Affibody molecules with reduced renal uptake

  • Article/chapterEnglish2008

Publisher, publication year, extent ...

  • 2008-07-02
  • Springer Science and Business Media LLC,2008
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-17054
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-17054URI
  • https://doi.org/10.1007/s00259-008-0845-7DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-9724URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

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

Notes

  • QC 20100716. Uppdaterad från in press till published (20100716).
  • Purpose  Affibody molecules are low molecular weight proteins (7 kDa), which can be selected to bind to tumour-associated target proteins with subnanomolar affinity. Because of rapid tumour localisation and clearance from nonspecific compartments, Affibody molecules are promising tracers for molecular imaging. Earlier, 99mTc-labelled Affibody molecules demonstrated specific targeting of tumour xenografts. However, the biodistribution was suboptimal either because of hepatobiliary excretion or high renal uptake of the radioactivity. The goal of this study was to optimise the biodistribution of Affibody molecules by chelator engineering. Materials and methods  Anti-HER2 ZHER2:342 Affibody molecules, carrying the mercaptoacetyl-glutamyl-seryl-glutamyl (maESE), mercaptoacetyl-glutamyl-glutamyl-seryl (maEES) and mercaptoacetyl-seryl-glutamyl-glutamyl (maSEE) chelators, were prepared by peptide synthesis and labelled with 99mTc. The tumour-targeting capacity of these conjugates was compared with each other and with the best previously available conjugate, 99mTc-maEEE-ZHER2:342, in nude mice bearing SKOV-3 xenografts. The tumour-targeting capacity of the most promising conjugate, 99mTc-maESE-ZHER2:342, was compared with radioiodinated ZHER2:342. Results  All novel conjugates demonstrated successful tumour targeting and a low degree of hepatobiliary excretion. The renal uptakes of serine-containing conjugates, 33 ± 5, 68 ± 21 and 71 ± 10%IA/g, for99mTc-maESE-ZHER2:342, 99mTc-maEES-ZHER2:342 and 99mTc-maSEE-ZHER2:342, respectively, were significantly reduced in comparison with 99mTc-maEEE-ZHER2:342 (102 ± 13%IA/g). For 99mTc-maESE-ZHER2:342, a tumour uptake of 9.6 ± 1.8%IA/g and a tumour-to-blood ratio of 58 ± 6 were reached at 4 h p.i. Conclusions  A combination of serine and glutamic acid residues in the chelator sequence confers increased renal excretion and relatively low renal uptake of 99mTc-labelled Affibody molecules. In combination with preserved targeting capacity, this improved imaging of targets in abdominal area.

Subject headings and genre

  • Affibody molecule
  • HER2
  • Renal uptake
  • Technetium-99m
  • Tumour targeting
  • MEDICINE
  • MEDICIN

Added entries (persons, corporate bodies, meetings, titles ...)

  • Tran, ThuyUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University (author)
  • Orlova, AnnaUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University(Swepub:uu)annaorlo (author)
  • Widström, CharlesUppsala universitet,Enheten för onkologi,Section of Hospital Physics, Department of Oncology, Uppsala University Hospital (author)
  • Feldwisch, JoachimUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University (author)
  • Abrahmsén, LarsAffibody AB, Bromma (author)
  • Wennborg, AndersAffibody AB, Bromma (author)
  • Eriksson Karlström, AmelieKTH,Skolan för bioteknologi (BIO)(Swepub:kth)u10x6l4n (author)
  • Tolmachev, VladimirUppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,Institutionen för medicinska vetenskaper,Unit of Nuclear Medicine, Department of Medical Sciences, Uppsala University(Swepub:uu)vladtolm (author)
  • KTHSkolan för bioteknologi (BIO) (creator_code:org_t)

Related titles

  • In:European Journal of Nuclear Medicine and Molecular Imaging: Springer Science and Business Media LLC35:12, s. 2245-22551619-70701619-7089

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