Evidence map›Paper›PMID 30148621›Full record

ArticleJournal of the American Chemical Society2018

CT Imaging of Enzymatic Activity in Cancer Using Covalent Probes Reveal a Size-Dependent Pattern.

Darya Tsvirkun, Yael Ben-Nun, Emmanuelle Merquiol, Ivan Zlotver, Karen Meir, Tommy Weiss-Sadan, Ilan Matok, Rachela Popovtzer, Galia Blum

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

32 citing papers in PubMed, 72 citations in OpenAlex.

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  3. Contrast Agents for Enhanced Bioimaging: A Comprehensive Review.Chembiochem : a European journal of chemical biology · 2026
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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

9 authors at 3 institutions in 1 country.

Darya TsvirkunThe Institute for Drug Research, The School of Pharmacy, The Faculty of Medicine, Campus Ein Karem , The Hebrew University , Jerusalem 9112001 , Israel.
Yael Ben-NunThe Institute for Drug Research, The School of Pharmacy, The Faculty of Medicine, Campus Ein Karem , The Hebrew University , Jerusalem 9112001 , Israel.
Emmanuelle MerquiolThe Institute for Drug Research, The School of Pharmacy, The Faculty of Medicine, Campus Ein Karem , The Hebrew University , Jerusalem 9112001 , Israel.
Ivan ZlotverThe Institute for Drug Research, The School of Pharmacy, The Faculty of Medicine, Campus Ein Karem , The Hebrew University , Jerusalem 9112001 , Israel.
Karen MeirDepartment of Pathology , Hadassah Medical Center , Jerusalem 9112001 , Israel.
Tommy Weiss-SadanThe Institute for Drug Research, The School of Pharmacy, The Faculty of Medicine, Campus Ein Karem , The Hebrew University , Jerusalem 9112001 , Israel.
Ilan MatokThe Institute for Drug Research, The School of Pharmacy, The Faculty of Medicine, Campus Ein Karem , The Hebrew University , Jerusalem 9112001 , Israel.
Rachela PopovtzerFaculty of Engineering & The Institute of Nanotechnology and Advanced Materials , Bar-Ilan University , Ramat Gan 52900 , Israel.
Galia BlumThe Institute for Drug Research, The School of Pharmacy, The Faculty of Medicine, Campus Ein Karem , The Hebrew University , Jerusalem 9112001 , Israel.ORCID 0000-0002-9374-2489
Hebrew University of Jerusalem · ILBar-Ilan University · ILHadassah Medical Center · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

X-ray CT instruments are among the most available, efficient, and cost-effective imaging modalities in hospitals. The field of CT molecular imaging is emerging which relies mainly on the detection of gold nanoparticles and iodine-containing compounds directed to tagging a variety of abundant biomolecules. Here for the first time we attempted to detect enzymatic activity, while the low sensitivity of CT scanners to contrast reagents made this a challenging task. Therefore, we developed a new class of nanosized cathepsin-targeted activity-based probes (ABPs) for functional CT imaging of cancer. ABPs are small molecules designed to covalently modify enzyme targets in an activity-dependent manner. Using a CT instrument, these novel probes enable detection of the elevated cathepsin activity within cancerous tissue, thus creating a direct link between biological processes and imaging signals. We present the generation and biochemical evaluation of a library of ABPs tagged with different sized gold nanoparticles (GNPs), with various ratios of cathepsin-targeting moiety and a combination of different polyethylene glycol (PEG) protective layers. The most potent and stable GNP-ABPs were applied for noninvasive cancer imaging in mice. Surprisingly, detection of CT contrast from the tumor had reverse correlation to GNP size and the amount of targeting moiety. Interestingly, TEM images of tumor sections show intercellular lysosomal subcellular localization of the GNP-ABPs. In conclusion, we demonstrate that the covalent linkage is key for detection using low sensitive imaging modalities and the utility of GNP-ABPs as a promising tool for enzymatic-based CT imaging.

Indexed as

AnimalsCathepsin BCell Line, TumorDipeptidesEnzyme InhibitorsGoldHumansLysosomesMaleMetal NanoparticlesMiceMice, Inbred BALB CNeoplasmsNIH 3T3 CellsPolyethylene GlycolsTomography, X-Ray ComputedCathepsin BDipeptidesEnzyme InhibitorsGoldPolyethylene Glycols

Identifiers

PMID30148621
PMCPMC6192666
OpenAlexW2888775013

What OpenQuestion holds

Textmetadata
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.