Claudio Vinegoni, Ph.D. | In vivo imaging of specific drug-target binding at subcellular resolution

Nat. Commun.
In vivo imaging of specific drug-target binding at subcellular resolution

Dubach^†, J. M., Vinegoni^#†, C., Mazitschek, R., Fumene Feruglio, P., Cameron, L. A., and Weissleder, R.

Nature Communications 2014

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The possibility of measuring binding of small-molecule drugs to desired targets in live cells could provide a better understanding of drug action. However, current approaches mostly yield static data, require lysis or rely on indirect assays and thus often provide an incomplete understanding of drug action. Here, we present a multiphoton fluorescence anisotropy microscopy live cell imaging technique to measure and map drug-target interaction in real time at subcellular resolution. This approach is generally applicable using any fluorescently labelled drug and enables high-resolution spatial and temporal mapping of bound and unbound drug distribution. To illustrate our approach we measure intracellular target engagement of the chemotherapeutic Olaparib, a poly(ADP-ribose) polymerase inhibitor, in live cells and within a tumour in vivo. These results are the first generalizable approach to directly measure drug-target binding in vivo and present a promising tool to enhance understanding of drug activity.
@article{2014-NC, author= {Dubach<sup>†</sup>, J. M. and Vinegoni<sup>#†</sup>, C. and Mazitschek, R. and Fumene Feruglio, P. and Cameron, L. A. and Weissleder, R.}, title= {In vivo imaging of specific drug-target binding at subcellular resolution}, journal= {Nature Communications}, alternatejournal = {Nat. Commun.}, year = {2014}, volume = {5}, pages = {9}, issn = {2041-1723}, doi = {10.1038/ncomms4946}, pmcid = {PMC4362617}, pmid= {24867710} }
24867710

PMC4362617

10.1038/ncomms4946

Abstract

"The possibility of measuring binding of small-molecule drugs to desired targets in live cells could provide a better understanding of drug action. However, current approaches mostly yield static data, require lysis or rely on indirect assays and thus often provide an incomplete understanding of drug action. Here, we present a multiphoton fluorescence anisotropy microscopy live cell imaging technique to measure and map drug-target interaction in real time at subcellular resolution. This approach is generally applicable using any fluorescently labelled drug and enables high-resolution spatial and temporal mapping of bound and unbound drug distribution. To illustrate our approach we measure intracellular target engagement of the chemotherapeutic Olaparib, a poly(ADP-ribose) polymerase inhibitor, in live cells and within a tumour in vivo. These results are the first generalizable approach to directly measure drug-target binding in vivo and present a promising tool to enhance understanding of drug activity."

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For attribution in academic contexts, please cite this work as:

Dubach^†, J. M., Vinegoni^#†, C., Mazitschek, R., Fumene Feruglio, P., Cameron, L. A., & Weissleder, R. (2014). In vivo imaging of specific drug-target binding at subcellular resolution. Nature Communications, 5, 9. https://doi.org/10.1038/ncomms4946