Tailoring Fluorescent Dyes To Optimize a Hybrid RGD-Tracer
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- 作者：Anton Bunschoten ; Danny M. van Willigen ; Tessa Buckle ; Nynke S. van den Berg ; Mick M. Welling ; Silvia J. Spa ; Hans-Jürgen Wester ; Fijs W. B. van Leeuwen
- 刊名：Bioconjugate Chemistry
- 出版年：2016
- 出版时间：May 18, 2016
- 年：2016
- 卷：27
- 期：5
- 页码：1253-1258
- 全文大小：466K
- 年卷期：0
- ISSN：1520-4812
文摘
Quantitative assessment of affinity and kinetics is a critical component in the development of (receptor-targeted) radiotracers. For fluorescent tracers, such an assessment is currently not yet applied, while (small) changes in chemical composition of the fluorescent component might have substantial influence on the overall properties of a fluorescent tracer. Hybrid imaging labels that contain both a radiolabel and a fluorescent dye can be used to evaluate both the affinity (fluorescent label) and the in vivo distribution (radiolabel) of a targeted tracer. We present a hybrid label oriented and matrix-based scoring approach that enabled quantitative assessment of the influence of (overall) charge and lipophilicity of the fluorescent label on the (in vivo) characteristics of αvβ3-integrin targeted tracers. Systematic chemical alterations in the fluorescent dye were shown to result in a clear difference in the in vivo distribution of the different hybrid tracers. The applied evaluation technique resulted in an optimized targeted tracer for αvβ3-integrin, which combined the highest T/M ratio with the lowest uptake in other organs. Obviously this selection concept would also be applicable during the development of other (receptor-targeted) imaging tracers.