Evidence map›Paper›PMID 23422672›Full record

ArticleNature communications2013

Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo.

Greg M Thurber, Katy S Yang, Thomas Reiner, Rainer H Kohler, Peter Sorger, Tim Mitchison, Ralph Weissleder

Abstract read
In one paragraph

Article in Nature communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

125 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Multidimensional Imaging of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023
    Review
  18. Article
  19. In Vivo Click Chemistry Enables Multiplexed Intravital Microscopy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Article
  20. Review

65 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Greg M ThurberCenter for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, Massachusetts 02114, USA.
Katy S Yang
Thomas Reiner
Rainer H Kohler
Peter Sorger
Tim Mitchison
Ralph Weissleder

Funding

StatisticsP50CA086355 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2000 to 2015
$27.8M
Training Grant in Molecular Imaging Research (MGH/HMS)T32CA079443 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2000 to 2025
$10.1M
Quantitative Analysis of Cell Death Pathways in CancerP01CA139980 · NCI · HARVARD MEDICAL SCHOOL · PI MITCHISON, TIMOTHY J · 2010 to 2014
$9.0M
Quantitative analysis of pharmacological mechanism by intravital imagingR01CA164448 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2011 to 2015
$4.0M
Whole Body Imaging of Beta Cell Mass in DiabetesK01DK093766 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THURBER, GREG · 2011 to 2014
$641k
Intravital microscopy imaging systemS10RR026360 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2010 to 2010
$500k
NCI NIH HHS 1R01CA164448NCI NIH HHS P01 CA139980NCI NIH HHS P01CA139980NCI NIH HHS P50 CA086355NCI NIH HHS P50CA086355NCI NIH HHS R01 CA164448NCI NIH HHS T32 CA079443NCRR NIH HHS S10 RR026360NIDDK NIH HHS K01 DK093766NIDDK NIH HHS K01DK093766
6 · The paper itself

Abstract

Pharmacokinetic analysis at the organ level provides insight into how drugs distribute throughout the body, but cannot explain how drugs work at the cellular level. Here we demonstrate in vivo single-cell pharmacokinetic imaging of PARP-1 inhibitors and model drug behaviour under varying conditions. We visualize intracellular kinetics of the PARP-1 inhibitor distribution in real time, showing that PARP-1 inhibitors reach their cellular target compartment, the nucleus, within minutes in vivo both in cancer and normal cells in various cancer models. We also use these data to validate predictive finite element modelling. Our theoretical and experimental data indicate that tumour cells are exposed to sufficiently high PARP-1 inhibitor concentrations in vivo and suggest that drug inefficiency is likely related to proteomic heterogeneity or insensitivity of cancer cells to DNA-repair inhibition. This suggests that single-cell pharmacokinetic imaging and derived modelling improve our understanding of drug action at single-cell resolution in vivo.

Indexed as

AnimalsCell Line, TumorComputer SimulationEnzyme InhibitorsFinite Element AnalysisHumansMiceModels, BiologicalMolecular ImagingNeoplasmsPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesReproducibility of ResultsSingle-Cell AnalysisSmall Molecule LibrariesSubcellular FractionsEnzyme InhibitorsPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesSmall Molecule Libraries

Identifiers

PMID23422672
PMCPMC3579506

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.