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European Journal of Nuclear Medicine and Molecular Imaging

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01-04-2012 | Original Article

Direct comparison of ¹¹¹In-labelled two-helix and three-helix Affibody molecules for in vivo molecular imaging

Authors: Daniel Rosik, Anna Orlova, Jennie Malmberg, Mohamed Altai, Zohreh Varasteh, Mattias Sandström, Amelie Eriksson Karlström, Vladimir Tolmachev

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2012

Abstract

Purpose

Radiolabelled Affibody molecules have demonstrated a potential for visualization of tumour-associated molecular targets. Affibody molecules (7 kDa) are composed of three alpha-helices. Recently, a smaller two-helix variant of Affibody molecules (5.1 kDa) was developed. The aim of this study was to compare two- and three-helix HER2-targeting Affibody molecules directly in vivo.

Methods

The three-helix Affibody molecule ABY-002 and the two-helix Affibody molecule PEP09239 were labelled with ¹¹¹In at the N-termini via DOTA chelator. Tumour-targeting properties were directly compared at 1 and 4 h after injection in mice bearing SKOV-3 xenografts with high HER2 expression and LS174T xenografts with low HER2 expression.

Results

The dissociation constants (K _D) for HER2 binding were 78 pM for the three-helix Affibody molecule and 2.1 nM for the two-helix Affibody molecule. ¹¹¹In-PEP09239 cleared more rapidly from the blood. In xenografts with high HER2 expression, the uptake of ¹¹¹In-ABY-002 was significantly higher than that of ¹¹¹In-PEP09239. The tumour-to-blood ratio was higher for ¹¹¹In-PEP09239 at 4 h after injection, while there was no significant difference in other tumour-to-organ ratios. The tumour uptake of ¹¹¹In-ABY-002 was eightfold higher than that of ¹¹¹In-PEP09239 in xenografts with low expression. Tumour-to-blood ratios were equal in this case, but other tumour-to-organ ratios were appreciably higher for the three-helix variant.

Conclusion

For tumours with high HER2 expression, two-helix HER2-targeting Affibody molecules can provide higher tumour-to-blood ratio at the cost of lower tumour uptake. In the case of low expression, both tumour uptake and tumour-to-organ ratios are appreciably higher for three-helix than for two-helix HER2-targeting Affibody molecules.

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Title: Direct comparison of 111In-labelled two-helix and three-helix Affibody molecules for in vivo molecular imaging
Authors: Daniel Rosik
Anna Orlova
Jennie Malmberg
Mohamed Altai
Zohreh Varasteh
Mattias Sandström
Amelie Eriksson Karlström
Vladimir Tolmachev
Publication date: 01-04-2012
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2012
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-011-2016-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Direct comparison of ¹¹¹In-labelled two-helix and three-helix Affibody molecules for in vivo molecular imaging

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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