Evidence map›Paper›PMID 24249640›Full record

ArticleMolecular imaging and biology2014

Examining changes in [18 F]FDG and [18 F]FLT uptake in U87-MG glioma xenografts as early response biomarkers to treatment with the dual mTOR1/2 inhibitor AZD8055.

Heather G Keen, Sally-Ann Ricketts, Juliana Maynard, Armelle Logie, Rajesh Odedra, Aoife M Shannon, Stephen R Wedge, Sylvie M Guichard

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In one paragraph

Article in Molecular imaging and biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Molecularly targeted therapies in cancer: a guide for the nuclear medicine physician.European journal of nuclear medicine and molecular imaging · 2017
    Review
  4. Article
  5. Experimental and therapeutic medicine · 2016
    Article
  6. Article
  7. Review
  8. 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 2 countries.

Heather G KeenPersonalised Healthcare and Biomarkers, AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK, heather.keen@astrazeneca.com.
Sally-Ann Ricketts
Juliana Maynard
Armelle Logie
Rajesh Odedra
Aoife M Shannon
Stephen R Wedge
Sylvie M Guichard
AstraZeneca (United Kingdom) · GBCancer Trials Ireland · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe mTOR kinase inhibitor AZD8055 inhibits both mTORC1 and mTORC2 leading to disruption of glucose metabolism and proliferation pathways. This study assessed the impact of single and multiple doses of AZD8055 on the uptake of the glucose metabolism marker 2-deoxy-2-[(18) F]fluoro-D-glucose ([(18) F]FDG) and the proliferation marker 3'-deoxy-3'-[(18) F]fluorothymidine ([(18) F]FLT) in U87-MG glioma xenografts. PROCEDURES: Mice bearing U87-MG tumours received either vehicle or AZD8055 (20 mg/kg) once daily p.o. Mice were imaged with either [(18) F]FDG or [(18) F]FLT PET to assess treatment response. Comparisons were made between in vivo imaging and ex vivo histopathology data.

resultsTumour uptake of [(18) F]FDG was reduced by 33 % 1 h after a single dose of AZD8055 and by 49 % following 4 days of dosing. These changes coincided with suppression of the mTOR pathway biomarkers pS6 and pAKT. In contrast, the effect of AZD8055 on [(18) F]FLT uptake was inconsistent.

conclusionsThe very rapid change in [(18) F]FDG uptake following acute AZD8055 treatment suggests that this could be used as an early mechanistic biomarker of metabolic changes resulting from mTOR inhibition. The utility of [(18) F]FLT for measuring the anti-proliferative effect of AZD8055 remains unclear.

Indexed as

AnimalsBiomarkers, TumorBrain NeoplasmsFemaleFluorodeoxyglucose F18GliomaHumansMiceMice, NudeMorpholinesTOR Serine-Threonine KinasesVascular Endothelial Growth Factor Receptor-1(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanolBiomarkers, TumorFLT1 protein, humanFluorodeoxyglucose F18MorpholinesTOR Serine-Threonine KinasesVascular Endothelial Growth Factor Receptor-1

Identifiers

PMID24249640
OpenAlexW2075883917

What OpenQuestion holds

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Registered trials

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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.