Evidence map›Paper›PMID 21586614›Full record

ArticleCancer research2011

Imaging DNA damage in vivo using gammaH2AX-targeted immunoconjugates.

Bart Cornelissen, Veerle Kersemans, Sonali Darbar, James Thompson, Ketan Shah, Kate Sleeth, Mark A Hill, Katherine A Vallis

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
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

38 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Molecular Imaging of p53 in Mouse Models of Cancer Using a Radiolabeled Antibody TAT Conjugate with SPECT.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024
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  7. Peptides for trans-blood-brain barrier delivery.Journal of labelled compounds & radiopharmaceuticals · 2023
    Review
  8. Review
  9. Article
  10. Article
  11. [Scientific reports · 2022
    Article
  12. Article
  13. A Model System to Explore the Detection Limits of Antibody-Based Immuno-SPECT Imaging of Exclusively Intranuclear Epitopes.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021
    Article
  14. Interest and Limits of [Frontiers in oncology · 2021
    Review
  15. Early Detection in a Mouse Model of Pancreatic Cancer by Imaging DNA Damage Response Signaling.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020
    Article
  16. Imaging DNA Damage Repair In Vivo AfterJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2020
    Article
  17. Theranostics · 2020
    Article
  18. Probing the limits of Q-tag bioconjugation of antibodies.Chemical communications (Cambridge, England) · 2019
    Article
  19. PET Imaging of PARP Expression UsingJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019
    Article
  20. Review
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

8 authors at 2 institutions in 1 country.

Bart CornelissenCR-UK/MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, United Kingdom.
Veerle Kersemans
Sonali Darbar
James Thompson
Ketan Shah
Kate Sleeth
Mark A Hill
Katherine A Vallis
University of Oxford · GBCRUK/MRC Oxford Institute for Radiation Oncology · GB

Funding

Cancer Research UK 11564Cancer Research UK A6245Cancer Research UK C14521/A6245Medical Research Council
6 · The paper itself

Abstract

DNA damage responses (DDR) occur during oncogenesis and therapeutic responses to DNA damaging cytotoxic drugs. Thus, a real-time method to image DNA damage in vivo would be useful to diagnose cancer and monitor its treatment. Toward this end, we have developed fluorophore- and radioisotope-labeled immunoconjugates to target a DDR signaling protein, phosphorylated histone H2A variant H2AX (γH2AX), which forms foci at sites of DNA double-strand breaks. Anti-γH2AX antibodies were modified by the addition of diethylenetriaminepentaacetic acid (DTPA) to allow (111)In labeling or the fluorophore Cy3. The cell-penetrating peptide Tat (GRKKRRQRRRPPQGYG) was also added to the immunoconjugate to aid nuclear translocation. In irradiated breast cancer cells, confocal microscopy confirmed the expected colocalization of anti-γH2AX-Tat with γH2AX foci. In comparison with nonspecific antibody conjugates, (111)In-anti-γH2AX-Tat was retained longer in cells. Anti-γH2AX-Tat probes were also used to track in vivo DNA damage, using a mouse xenograft model of human breast cancer. After local X-ray irradiation or bleomycin treatment, the anti-γH2AX-Tat probes produced fluorescent and single photon emission computed tomography signals in the tumors that were proportionate to the delivered radiation dose and the amount of γH2AX present. Taken together, our findings establish the use of radioimmunoconjugates that target γH2AX as a noninvasive imaging method to monitor DNA damage, with many potential applications in preclinical and clinical settings.

Indexed as

DNA DamageAmino Acid SequenceAnimalsAntibodiesBreast NeoplasmsCarbocyaninesCell Line, TumorDNA, NeoplasmFemaleGene Products, tatHistonesHumansImmunoconjugatesIndium RadioisotopesMiceMice, Inbred BALB CAntibodiesCarbocyaninescyanine dye 3DNA, NeoplasmGene Products, tatH2AX protein, humanHistonesImmunoconjugatesIndium RadioisotopesPentetic Acid

Identifiers

PMID21586614
PMCPMC3130133
OpenAlexW2100483345

What OpenQuestion holds

Textmetadata
LicenceTDM
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.