Fluorescence anisotropy imaging in drug discovery

Claudio Vinegoni; Paolo Fumene Feruglio; Ignacy Gryczynski; Ralph Mazitschek; Ralph Weissleder

doi:10.1016/j.addr.2018.01.019

Fluorescence anisotropy imaging in drug discovery

Adv Drug Deliv Rev. 2019 Nov-Dec:151-152:262-288. doi: 10.1016/j.addr.2018.01.019. Epub 2018 Feb 2.

Authors

Claudio Vinegoni¹, Paolo Fumene Feruglio², Ignacy Gryczynski³, Ralph Mazitschek⁴, Ralph Weissleder⁴

Affiliations

¹ Center for System Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: cvinegoni@mgh.harvard.edu.
² Center for System Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
³ University of North Texas Health Science Center, Institute for Molecular Medicine, Fort Worth, TX, United States.
⁴ Center for System Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Abstract

Non-invasive measurement of drug-target engagement can provide critical insights in the molecular pharmacology of small molecule drugs. Fluorescence polarization/fluorescence anisotropy measurements are commonly employed in protein/cell screening assays. However, the expansion of such measurements to the in vivo setting has proven difficult until recently. With the advent of high-resolution fluorescence anisotropy microscopy it is now possible to perform kinetic measurements of intracellular drug distribution and target engagement in commonly used mouse models. In this review we discuss the background, current advances and future perspectives in intravital fluorescence anisotropy measurements to derive pharmacokinetic and pharmacodynamic measurements in single cells and whole organs.

Keywords: Drug-target engagement; Fluorescence anisotropy imaging; Fluorescence polarization, fluorescence anisotropy; Fluorescently labeled drugs; Intravital imaging; Single-cell pharmacodynamics; Two photon microscopy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Drug Discovery*
Fluorescence Polarization*
High-Throughput Screening Assays
Humans

Abstract

Publication types

MeSH terms

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