Evidence map›Paper›PMID 27372286›Full record

ArticleNuclear medicine and biology2016

Imaging of hypoxia in mouse atherosclerotic plaques with (64)Cu-ATSM.

Xingyu Nie, Gwendalyn J Randolph, Andrew Elvington, Nilantha Bandara, Alexander Zheleznyak, Robert J Gropler, Pamela K Woodard, Suzanne E Lapi

Open access · greenAbstract read
In one paragraph

Article in Nuclear medicine and biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

5 citing papers in PubMed, 15 citations in OpenAlex.

  1. Polymeric Nanomaterials for Atherosclerosis Diagnosis and Treatment.Polymer science & technology (Washington, D.C.) · 2025
    Review
  2. Review
  3. Article
  4. Thrombus Formation and Propagation in the Onset of Cardiovascular Events.Journal of atherosclerosis and thrombosis · 2018
    Review
  5. PET Imaging of Cardiac Hypoxia: Hitting Hypoxia Where It Hurts.Current cardiovascular imaging reports · 2018
    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.

Xingyu NieMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO; Department of Biomedical Engineering, Washington University in St. Louis.
Gwendalyn J RandolphDivision of Biology and Biomedical Sciences, Washington University in St. Louis.
Andrew ElvingtonDivision of Biology and Biomedical Sciences, Washington University in St. Louis.
Nilantha BandaraMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO.
Alexander ZheleznyakMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO.
Robert J GroplerMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO.
Pamela K WoodardMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO; Department of Biomedical Engineering, Washington University in St. Louis; Diabetic Cardiovascular Disease Center, Washington University in St. Louis.
Suzanne E LapiMallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO; Division of Biology and Biomedical Sciences, Washington University in St. Louis; Department of Biomedical Engineering, Washington University in St. Louis. Electronic address: lapis@mir.wustl.edu.
Washington University in St. Louis · USMallinckrodt (United States) · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
PRINCIPLES IN CARDIVASCULAR RESEARCH TRAINING PROGRAMT32HL007081 · NHLBI · WASHINGTON UNIVERSITY · PI Abhinav Diwan, Karen Ellen Joynt Maddox · 1985 to 2026
$10.6M
NCATS NIH HHS UL1 TR000448NCI NIH HHS P30 CA091842NHLBI NIH HHS T32 HL007081
6 · The paper itself

Abstract

introductionCardiovascular disease is the leading cause of death in the United States. The identification of vulnerable plaque at risk of rupture has been a major focus of research. Hypoxia has been identified as a potential factor in the formation of vulnerable plaque, and it is clear that decreased oxygen plays a role in the development of plaque angiogenesis leading to plaque destabilization. The purpose of this study is to demonstrate the feasibility of copper-64 labeled diacetyl-bis (N(4)-methylthiosemicarbazone) ((64)Cu-ATSM), a positron-emitting radiopharmaceutical taken up in low-oxygen-tension cells, for the identification of hypoxic and potentially unstable atherosclerotic plaque in a mouse model.

methods(64)Cu-ATSM PET was performed in 21 atherosclerotic apolipoprotein E knockout (ApoE(-/-)) mice, 6 of which were fed high-fat diet (HFD) while the others received standard-chow diet (SCD), and 13 control wild type mice fed SCD. 4 SCD ApoE(-/-) mice and 4 SCD wild type mice also underwent (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) imaging one day prior to (64)Cu-ATSM PET.

results(64)Cu-ATSM uptake was increased in the aortic arch in SCD ApoE(-/-) mice (average aortic arch/muscle (A/M) standardized uptake value ratio 7.5-30min post injection: (5.66±0.23) compared to control mice (A/M SUV ratio 7.5-30min post injection (3.87±0.22), p<0.0001). HFD ApoE(-/-) mice also showed similarly increased aortic arch uptake on PET imaging in comparison to control mice. Immunohistochemistry in both HFD and SCD ApoE(-/-) mice revealed noticeable hypoxia by pimonidazole stain in atherosclerosis which was co-localized to macrophage by CD68 staining. Autoradiography assessment demonstrated the presence of hypoxia by (64)Cu-ATSM uptake correlated with pimonidazole uptake within the ex vivo atherosclerotic aortic arch specimens. A significant increase in (18)F-FDG uptake in the SCD ApoE(-/-) mice in comparison to controls was also observed at delayed time points.

conclusionThis pre-clinical study suggests that (64)Cu-ATSM is a potential PET tracer for hypoxia imaging in atherosclerosis. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: While studies in humans are necessary for conclusive data, in the long term, a (64)Cu-ATSM PET imaging strategy could help facilitate the study of plaque biology in human patients.

Indexed as

Organometallic CompoundsPositron-Emission TomographyThiosemicarbazonesAnimalsBiological TransportCell HypoxiaCoordination ComplexesImage Processing, Computer-AssistedMiceMice, Inbred C57BLPlaque, AtheroscleroticCoordination Complexescopper (II) diacetyl-di(N(4)-methylthiosemicarbazone)Organometallic CompoundsThiosemicarbazonesApo EAtherosclerosisCopper-64Cu-ATSMHypoxia

Identifiers

PMID27372286
PMCPMC4992634
OpenAlexW2409791630

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.