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Keywords
(5)
Radionuclide Imaging
trastuzumab
High Sensitivity
Injected Dose
Specific Activity
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Optimal specific radioactivity of anti-HER2 Affibody molecules enables discrimination between xenografts with high and low HER2 expression levels
Optimal specific radioactivity of anti-HER2 Affibody molecules enables discrimination between xenografts with high and low HER2 expression levels,10.1
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Optimal specific radioactivity of anti-HER2 Affibody molecules enables discrimination between xenografts with high and low HER2 expression levels
(
Citations: 2
)
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Vladimir Tolmachev
,
Helena Wållberg
,
Mattias Sandström
,
Monika Hansson
,
Anders Wennborg
,
Anna Orlova
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.
Journal:
European Journal of Nuclear Medicine and Molecular Imaging - EUR J NUCL MED MOL IMAGING
, vol. 38, no. 3, pp. 531-539, 2011
DOI:
10.1007/s00259-010-1646-3
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(1)
...,
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Greg Michael Thurber
,
et al.
A Systems Approach for Tumor Pharmacokinetics
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A Systems Approach for Tumor Pharmacokinetics
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