Influence of valency and labelling chemistry on in vivo targeting using radioiodinated HER2-binding Affibody molecules

Eur J Nucl Med Mol Imaging. 2009 Apr;36(4):692-701. doi: 10.1007/s00259-008-1003-y. Epub 2008 Dec 10.


Purpose: HER2 is a transmembrane tyrosine kinase, which is overexpressed in a number of carcinomas. The Affibody molecule Z(HER2:342) is a small (7 kDa) affinity protein binding to HER2 with an affinity of 22 pM. The goal of this study was to evaluate the use of ((4-hydroxyphenyl)ethyl)maleimide (HPEM) for radioiodination of Z(HER2:342) and to compare the targeting properties of monomeric and dimeric forms of Z(HER2:342).

Methods: The biodistribution of different radioiodinated derivatives of Z(HER2:342) was studied in BALB/C nu/nu mice bearing HER2-expressing SKOV-3 xenografts. Biodistributions of (125)I-PIB-Z(HER2:342) and site-specifically labelled (125)I-HPEM-Z(HER2:342)-C were compared. Biodistributions of monomeric (131)I-HPEM-Z(HER2:342)-C and dimeric (125)I-HPEM-(Z(HER2:342))(2)-C were evaluated using a paired-label method.

Results: (125)I-HPEM-Z(HER2:342)-C had the same level of tumour accumulation as (125)I-PIB-Z(HER2:342), but fourfold lower renal retention of radioactivity. The monomeric form of Z(HER2:342) provided better tumour targeting than the dimeric form.

Conclusion: Favourable biodistribution of (131)I-HPEM-Z(HER2:342)-C makes it a promising candidate for radionuclide therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dimerization
  • Female
  • Humans
  • Iodine Radioisotopes / pharmacology*
  • Kidney / diagnostic imaging
  • Mice
  • Mice, Inbred BALB C
  • Models, Chemical
  • Neoplasm Transplantation
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacology*
  • Receptor, ErbB-2 / chemistry*
  • Receptor, ErbB-2 / metabolism
  • Tissue Distribution


  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Receptor, ErbB-2