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dc.contributor.authorThurber, Greg M.
dc.contributor.authorReiner, Thomas
dc.contributor.authorYang, Katherine S.
dc.contributor.authorKohler, Rainer
dc.contributor.authorWeissleder, Ralph
dc.date.accessioned2019-09-21T03:36:26Z
dc.date.issued2014
dc.identifier.citationThurber, G. M., T. Reiner, K. S. Yang, R. H. Kohler, and R. Weissleder. 2014. “Effect of Small-Molecule Modification on Single-Cell Pharmacokinetics of PARP Inhibitors.” Molecular Cancer Therapeutics 13 (4): 986–95. https://doi.org/10.1158/1535-7163.mct-13-0801.
dc.identifier.issn1535-7163
dc.identifier.issn1538-8514
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41384289*
dc.description.abstractThe 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, wefollowed 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. Mol Cancer Ther; 13(4); 986-95. (C)2014 AACR.
dc.language.isoen_US
dc.publisherAmerican Association for Cancer Research
dash.licenseLAA
dc.titleEffect of Small Molecule Modification on Single Cell Pharmacokinetics of PARP Inhibitors
dc.typeJournal Article
dc.description.versionAccepted Manuscript
dc.relation.journalMolecular Cancer Therapeutics
dash.depositing.authorWeissleder, Ralph::ea07ce19f187d4fab47c56ee97fa5c5a::600
dc.date.available2019-09-21T03:36:26Z
dash.workflow.comments1Science Serial ID 65442
dc.identifier.doi10.1158/1535-7163.MCT-13-0801
dash.source.volume13;4
dash.source.page986


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