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Optimal specific radioactivity of anti-HER2 Affibody molecules enables discrimination between xenografts with high and low HER2 expression levels

European Journal of Nuclear Medicine and Molecular Imaging volume 38, pages 531–539 (2011)Cite this article

Abstract

Purpose

Overexpression of the HER2 receptor is a biomarker for predicting those patients who may benefit from trastuzumab therapy. Radiolabelled Affibody molecules can be used to visualize HER2 expression in tumour xenografts with high sensitivity. However, previous studies demonstrated that the difference in uptake in xenografts with high and low HER2 expression levels is not proportional to the difference in expression levels. We hypothesized that discrimination between tumours with high and low HER2 expression may be improved by increasing the injected dose (reducing the specific activity) of the tracer.

Methods

The influence of injected dose of anti-HER2 111In-DOTA-ZHER2 342 Affibody molecule on uptake in SKOV-3 (high HER2 expression) and LS174T (low expression) xenografts was investigated. The optimal range of injected doses enabling discrimination between xenografts with high and low expression was determined. To verify this, tumour uptake was measured in mice carrying both SKOV-3 and LS174T xenografts after injection of either 1 or 15 μg 111In-DOTA-ZHER2:342.

Results

An increase in the injected dose caused a linear decrease in the radioactivity accumulation in the LS174T xenografts (low HER2 expression). For SKOV-3 xenografts, the dependence of the tumour uptake on the injected dose was less dramatic. The injection of 10–30 μg 111In-DOTA-ZHER2:342 per mouse led to the largest difference in uptake between the two types of tumour. Experiments in mice bearing two xenografts confirmed that the optimized injected dose enabled better discrimination of expression levels.

Conclusion

Careful optimization of the injected dose of Affibody molecules is required for maximum discrimination between xenografts with high and low levels of HER2 expression. This information has potential relevance for clinical imaging applications.

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Acknowledgments

This study was supported by grants from the Swedish Cancer Society (Cancerfonden) and the Swedish Research Council (Vetenskapsrådet).

Conflicts of interest

AW has an affiliation (employment) with Affibody AB, Stockholm, Sweden, which holds the intellectual property rights and trademarks for Affibody molecules.

Author information

Affiliations

  1. Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, 751 81, Uppsala, Sweden

    Vladimir Tolmachev & Anna Orlova

  2. Department of Medical Sciences, Nuclear Medicine, Uppsala University, Uppsala, Sweden

    Vladimir Tolmachev

  3. School of Biotechnology, Royal Institute of Technology, Stockholm, Sweden

    Helena Wållberg

  4. Section of Hospital Physics, Department of Oncology, Uppsala University Hospital, Uppsala, Sweden

    Mattias Sandström

  5. Affibody AB, Stockholm, Sweden

    Monika Hansson & Anders Wennborg

Authors
  1. Vladimir Tolmachev
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  2. Helena Wållberg
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  3. Mattias Sandström
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  4. Monika Hansson
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  5. Anders Wennborg
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  6. Anna Orlova
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Corresponding author

Correspondence to Vladimir Tolmachev.

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Tolmachev, V., Wållberg, H., Sandström, M. et al. Optimal specific radioactivity of anti-HER2 Affibody molecules enables discrimination between xenografts with high and low HER2 expression levels. Eur J Nucl Med Mol Imaging 38, 531–539 (2011). https://doi.org/10.1007/s00259-010-1646-3

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  • DOI: https://doi.org/10.1007/s00259-010-1646-3

Keywords

  • Affibody molecules
  • HER2
  • Specific activity
  • Radionuclide imaging
  • Indium-111