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

Vladimir Tolmachev, Eskender Mume, Stefan Sjöberg, Fredrik Y. Frejd, Anna Orlova

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

Purpose: HER2 is a transmembrane tyrosine kinase, which is overexpressed in a number of carcinomas. The Affibody molecule ZHER2:342 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 ZHER2:342 and to compare the targeting properties of monomeric and dimeric forms of ZHER2:342. Methods: The biodistribution of different radioiodinated derivatives of ZHER2:342 was studied in BALB/C nu/nu mice bearing HER2-expressing SKOV-3 xenografts. Biodistributions of 125I-PIB-ZHER2:342 and site-specifically labelled 125I-HPEM-ZHER2:342-C were compared. Biodistributions of monomeric 131I-HPEM-Z HER2:342-C and dimeric 125I-HPEM-(ZHER2:342) 2-C were evaluated using a paired-label method. Results: 125I-HPEM-ZHER2:342-C had the same level of tumour accumulation as 125I-PIB-ZHER2:342, but fourfold lower renal retention of radioactivity. The monomeric form of ZHER2:342 provided better tumour targeting than the dimeric form. Conclusion: Favourable biodistribution of 131I-HPEM-ZHER2:342-C makes it a promising candidate for radionuclide therapy.

Original languageEnglish
Pages (from-to)692-701
Number of pages10
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume36
Issue number4
DOIs
Publication statusPublished - Apr 2009
Externally publishedYes

Keywords

  • Affibody molecule
  • HER2
  • Iodine-131
  • Radionuclide therapy
  • Renal uptake

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Influence of valency and labelling chemistry on in vivo targeting using radioiodinated HER2-binding Affibody molecules'. Together they form a unique fingerprint.

Cite this