Effect of small-molecule modification on single-cell pharmacokinetics of PARP inhibitors Academic Article uri icon


MeSH Major

  • Enzyme Inhibitors
  • Phthalazines
  • Piperazines
  • Single-Cell Analysis


  • The heterogeneous delivery of drugs in tumors is an established process contributing to variability in treatment outcome. Despite the general acceptance of variable delivery, the study of the underlying causes is challenging, given the complex tumor microenvironment including intra- and intertumor heterogeneity. The difficulty in studying this distribution is even more significant for small-molecule drugs where radiolabeled compounds or mass spectrometry detection lack the spatial and temporal resolution required to quantify the kinetics of drug distribution in vivo. In this work, we take advantage of the synthesis of fluorescent drug conjugates that retain their target binding but are designed with different physiochemical and thus pharmacokinetic properties. Using these probes, we followed the drug distribution in cell culture and tumor xenografts with temporal resolution of seconds and subcellular spatial resolution. These measurements, including in vivo permeability of small-molecule drugs, can be used directly in predictive pharmacokinetic models for the design of therapeutics and companion imaging agents as demonstrated by a finite element model.

publication date

  • January 2014



  • Academic Article



  • eng

PubMed Central ID

  • PMC3981972

Digital Object Identifier (DOI)

  • 10.1158/1535-7163.MCT-13-0801

PubMed ID

  • 24552776

Additional Document Info

start page

  • 986

end page

  • 95


  • 13


  • 4