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European Journal of Nuclear Medicine and Molecular Imaging

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01.04.2009 | Original Article

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

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

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 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 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 ¹²⁵I-PIB-Z_HER2:342 and site-specifically labelled ¹²⁵I-HPEM-Z_HER2:342-C were compared. Biodistributions of monomeric ¹³¹I-HPEM-Z_HER2:342-C and dimeric ¹²⁵I-HPEM-(Z_HER2:342)₂-C were evaluated using a paired-label method.

Results

¹²⁵I-HPEM-Z_HER2:342-C had the same level of tumour accumulation as ¹²⁵I-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 ¹³¹I-HPEM-Z_HER2:342-C makes it a promising candidate for radionuclide therapy.

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Titel: Influence of valency and labelling chemistry on in vivo targeting using radioiodinated HER2-binding Affibody molecules
verfasst von: Vladimir Tolmachev
Eskender Mume
Stefan Sjöberg
Fredrik Y. Frejd
Anna Orlova
Publikationsdatum: 01.04.2009
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 4/2009
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-008-1003-y

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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