Evidence map›Paper›PMID 25010662›Full record

ArticlePloS one2014

Investigation of a MMP-2 activity-dependent anchoring probe for nuclear imaging of cancer.

Takashi Temma, Hirofumi Hanaoka, Aki Yonezawa, Naoya Kondo, Kohei Sano, Takeharu Sakamoto, Motoharu Seiki, Masahiro Ono, Hideo Saji

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 39% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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.

Takashi TemmaDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Hirofumi HanaokaDepartment of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba, Japan.
Aki YonezawaDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Naoya KondoDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Kohei SanoDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan; Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
Takeharu SakamotoDivision of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Motoharu SeikiDivision of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Masahiro OnoDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Hideo SajiDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Kyoto University · JPThe University of Tokyo · JPChiba University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeSince matrix metalloproteinase-2 (MMP-2) is an important marker of tumor malignancy, we developed an original drug design strategy, MMP-2 activity dependent anchoring probes (MDAP), for use in MMP-2 activity imaging, and evaluated the usefulness of this probe in in vitro and in vivo experiments.

methodsWe designed and synthesized MDAP(1000), MDAP(3000), and MDAP(5000), which consist of 4 independent moieties: RI unit (111)In hydrophilic chelate), MMP-2 substrate unit (short peptide), anchoring unit (alkyl chain), and anchoring inhibition unit (polyethylene glycol (PEGn; where n represents the approximate molecular weight, n = 1000, 3000, and 5000). Probe cleavage was evaluated by chromatography after MMP-2 treatment. Cellular uptake of the probes was then measured. Radioactivity accumulation in tumor xenografts was evaluated after intravenous injection of the probes, and probe cleavage was evaluated in tumor homogenates.

resultsMDAP(1000), MDAP(3000), and MDAP(5000) were cleaved by MMP-2 in a concentration-dependent manner. MDAP(3000) pretreated with MMP-2 showed higher accumulation in tumor cells, and was completely blocked by additional treatment with an MMP inhibitor. MDAP(3000) exhibited rapid blood clearance and a high tumor accumulation after intravenous injection in a rodent model. Furthermore, pharmacokinetic analysis revealed that MDAP(3000) exhibited a considerably slow washout rate from tumors to blood. A certain fraction of cleaved MDAP(3000) existed in tumor xenografts in vivo.

conclusionsThe results indicate the possible usefulness of our MDAP strategy for tumor imaging.

Indexed as

Diagnostic ImagingMatrix Metalloproteinase InhibitorsAnimalsBiomarkers, TumorCell Line, TumorHumansInjections, IntravenousMatrix Metalloproteinase 2MiceNeoplasmsXenograft Model Antitumor AssaysBiomarkers, TumorMatrix Metalloproteinase 2Matrix Metalloproteinase Inhibitors

Identifiers

PMID25010662
PMCPMC4092090
OpenAlexW1987905008

What OpenQuestion holds

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LicenceCC BY
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.