Evidence map›Paper›PMID 28726131›Full record

ArticleMolecular imaging and biology2018

Detection of Enzyme Activity and Inhibition during Studies in Solution, In Vitro and In Vivo with CatalyCEST MRI.

Sanhita Sinharay, Edward A Randtke, Christine M Howison, Natalia A Ignatenko, Mark D Pagel

Abstract read
In one paragraph

Article in Molecular imaging and biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Induced volatolomics of pathologies.Nature reviews. Chemistry · 2021
    Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. 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

5 authors.

Sanhita SinharayDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
Edward A RandtkeDepartment of Medical Imaging, University of Arizona, 1515 N. Campbell Avenue, Tucson, AZ, 84724-5024, USA.
Christine M HowisonDepartment of Medical Imaging, University of Arizona, 1515 N. Campbell Avenue, Tucson, AZ, 84724-5024, USA.
Natalia A IgnatenkoDepartment of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA.
Mark D PagelDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA. mdpagel@mdanderson.org.

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Dan Theodorescu · 1985 to 2026
$110.2M
Detection of in vivo enzyme activities with CEST MRIR01CA169774 · NCI · UNIVERSITY OF ARIZONA · PI CARDENAS-RODRIGUEZ, JULIO · 2012 to 2016
$2.5M
Role of Kallikrein 6 expression and secretion in colon cancerR01CA157595 · NCI · UNIVERSITY OF ARIZONA · PI IGNATENKO, NATALIA A · 2012 to 2016
$1.7M
NCI NIH HHS P30 CA023074NCI NIH HHS R01 CA157595NCI NIH HHS R01 CA169774NIH HHS P30CA23074NIH HHS RO1CA157595NIH HHS RO1CA169774
6 · The paper itself

Abstract

purposeThe detection of enzyme activities and evaluation of enzyme inhibitors have been challenging with magnetic resonance imaging (MRI). To address this need, we have developed a diamagnetic, nonmetallic contrast agent and a protocol known as catalyCEST MRI that uses chemical exchange saturation transfer (CEST) to detect enzyme activity as well as enzyme inhibition. PROCEDURES: We synthesized a diamagnetic MRI contrast agent that has enzyme responsive and enzyme unresponsive CEST signals. We tested the ability of this agent to detect the activity of kallikrein 6 (KLK6) in biochemical solutions, in vitro and in vivo, with and without a KLK6 inhibitor.

resultsThe agent detected KLK6 activity in solution and also detected KLK6 inhibition by antithrombin III. KLK6 activity was detected during in vitro studies with HCT116 colon cancer cells, relative to the detection of almost no activity in a KLK6-knockdown HCT116 cell line and HCT116 cells treated with antithrombin III inhibitor. Finally, strong enzyme activity was detected within an in vivo HCT116 tumor model, while lower enzyme activity was detected in a KLK6 knockdown tumor model and in the HCT116 tumor model treated with antithrombin III inhibitor. In all cases, comparisons of the enzyme responsive and enzyme unresponsive CEST signals were critical for the detection of enzyme activity.

conclusionsThis study has established that catalyCEST MRI with an exogenous diaCEST agent can evaluate enzyme activity and inhibition in solution, in vitro and in vivo.

Indexed as

Magnetic Resonance ImagingEnzyme InhibitorsHCT116 CellsHumansKallikreinsSolutionsEnzyme InhibitorsKallikreinsKLK6 protein, humanSolutionsCEST MRIColon cancerEnzyme activityEnzyme inhibitionMolecular imaging

Identifiers

PMID28726131
PMCPMC6010181

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.