Direct imaging of drug distribution and target engagement of the PARP inhibitor rucaparib Academic Article uri icon

Overview

MeSH Major

  • Cyclohexenes
  • Phenylalanine
  • Ruthenium

abstract

  • © Copyright 2018 by the Society of Nuclear Medicine and Molecular Imaging. Poly(ADP-ribose)polymerase (PARP) inhibitors have emerged as potent antitumor drugs. Here, we describe the intrinsic fluorescence properties of the clinically approved PARP inhibitor rucaparib and its potential to directly measure drug distribution and target engagementa critical factor for understanding drug action and improving efficacy. Methods: We characterized the photophysical properties of rucaparib and determined its quantum yield and lifetime. Using confocal microscopy and flow cytometry, we imaged the intracellular distribution of rucaparib and measured uptake and release kinetics. Results: Rucaparib has an excitation/emission maximum of 355/480 nm and a quantum yield of 0.3. In vitro timelapse imaging showed accumulation in cell nuclei within seconds of administration. Nuclear rucaparib uptake increased with higher PARP1 expression, and we determined an intracellular half-life of 6.4 h. Conclusion: The label-free, intrinsic fluorescence of rucaparib can be exploited to interrogate drug distribution and target binding, critical factors toward improving treatment efficacy and outcome.

publication date

  • August 2018

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC6071506

Digital Object Identifier (DOI)

  • 10.2967/jnumed.117.205765

PubMed ID

  • 29572258

Additional Document Info

start page

  • 1316

end page

  • 1320

volume

  • 59

number

  • 8