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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 4/2009

01-04-2009 | Original Article

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

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

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2009

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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-ZHER2:342-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.
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Metadata
Title
Influence of valency and labelling chemistry on in vivo targeting using radioiodinated HER2-binding Affibody molecules
Authors
Vladimir Tolmachev
Eskender Mume
Stefan Sjöberg
Fredrik Y. Frejd
Anna Orlova
Publication date
01-04-2009
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2009
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-008-1003-y

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