PT  - JOURNAL ARTICLE
AU  - Susanne Kossatz
AU  - Brandon Carney
AU  - Christopher Farley
AU  - Wolfgang A. Weber
AU  - Charles M. Drain
AU  - Thomas Reiner
TI  - Direct Imaging of Drug Distribution and Target Engagement of the PARP Inhibitor Rucaparib
AID  - 10.2967/jnumed.117.205765
DP  - 2018 Aug 01
TA  - Journal of Nuclear Medicine
PG  - 1316--1320
VI  - 59
IP  - 8
4099  - http://jnm.snmjournals.org/content/59/8/1316.short
4100  - http://jnm.snmjournals.org/content/59/8/1316.full
SO  - J Nucl Med2018 Aug 01; 59
AB  - 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 engagement—a 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 time-lapse 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.