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

Vladimir Tolmachev, Helena Wållberg, Mattias Sandström, Monika Hansson, Anders Wennborg, Anna Orlova

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

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-Z HER2:342 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-DOTAZHER2:342 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.

Original languageEnglish
Pages (from-to)531-539
Number of pages9
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume38
Issue number3
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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