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Optimal specific radioactivity of anti-HER2 Affibody molecules enables discrimination between xenografts with high and low HER2 expression levels
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences. (BMS)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
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2011 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 38, no 3, 531-539 p.Article in journal (Refereed) Published
Abstract [en]

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. The influence of injected dose of anti-HER2 In-111-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 mu g In-111-DOTA-Z(HER2:342). 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 mu g In-111-DOTA-Z(HER2:342) 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. 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.

Place, publisher, year, edition, pages
2011. Vol. 38, no 3, 531-539 p.
Keyword [en]
Affibody molecules, HER2, Specific activity, Radionuclide imaging, Indium-111
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-148626DOI: 10.1007/s00259-010-1646-3ISI: 000287098000016PubMedID: 21069318OAI: oai:DiVA.org:uu-148626DiVA: diva2:402430
Available from: 2011-03-08 Created: 2011-03-08 Last updated: 2017-12-11Bibliographically approved

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Tolmachev, VladimirOrlova, Anna

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