Evidence map›Paper›PMID 25365349›Full record

ArticlePloS one2014

64Cu-DOTA-anti-CTLA-4 mAb enabled PET visualization of CTLA-4 on the T-cell infiltrating tumor tissues.

Kei Higashikawa, Katsuharu Yagi, Keiko Watanabe, Shinichiro Kamino, Masashi Ueda, Makoto Hiromura, Shuichi Enomoto

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 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

61 citing papers in PubMed, 111 citations in OpenAlex.

  1. Trial
  2. Imaging Immunotherapy.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2026
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  19. Imaging in Tumor Immunology.Nuclear medicine and molecular imaging · 2021
    Review
  20. Spatio-temporal biodistribution ofScientific reports · 2021
    Article

1 more citing papers are in PubMed but not listed here.

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

7 authors at 1 institution in 1 country.

Kei HigashikawaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Japan Society for the Promotion of Science, Tokyo, Japan.
Katsuharu YagiGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Keiko WatanabeGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Shinichiro KaminoNext-generation Imaging Team, RIKEN Center for Life Science Technologies, Kobe, Japan.
Masashi UedaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Makoto HiromuraNext-generation Imaging Team, RIKEN Center for Life Science Technologies, Kobe, Japan.
Shuichi EnomotoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Next-generation Imaging Team, RIKEN Center for Life Science Technologies, Kobe, Japan.
Okayama University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) targeted therapy by anti-CTLA-4 monoclonal antibody (mAb) is highly effective in cancer patients. However, it is extremely expensive and potentially produces autoimmune-related adverse effects. Therefore, the development of a method to evaluate CTLA-4 expression prior to CTLA-4-targeted therapy is expected to open doors to evidence-based and cost-efficient medical care and to avoid adverse effects brought about by ineffective therapy. In this study, we aimed to develop a molecular imaging probe for CTLA-4 visualization in tumor. First, we examined CTLA-4 expression in normal colon tissues, cultured CT26 cells, and CT26 tumor tissues from tumor-bearing BALB/c mice and BALB/c nude mice by reverse transcription polymerase chain reaction (RT-PCR) analysis and confirmed whether CTLA-4 is strongly expressed in CT26 tumor tissues. Second, we newly synthesized 64Cu-1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid-anti-mouse CTLA-4 mAb (64Cu-DOTA-anti-CTLA-4 mAb) and evaluated its usefulness in positron emission tomography (PET) and ex-vivo biodistribution analysis in CT26-bearing BALB/c mice. High CTLA-4 expression was confirmed in the CT26 tumor tissues of tumor-bearing BALB/c mice. However, CTLA-4 expression was extremely low in the cultured CT26 cells and the CT26 tumor tissues of tumor-bearing BALB/c nude mice. The results suggested that T cells were responsible for the high CTLA-4 expression. Furthermore, 64Cu-DOTA-anti-CTLA-4 mAb displayed significantly high accumulation in the CT26 tumor, thereby realizing non-invasive CTLA-4 visualization in the tumor. Together, the results indicate that 64Cu-DOTA-anti-CTLA-4 mAb would be useful for the evaluation of CTLA-4 expression in tumor.

Indexed as

Antibodies, MonoclonalCopper RadioisotopesOrganometallic CompoundsPositron-Emission TomographyAnimalsCell Line, TumorCTLA-4 AntigenDisease Models, AnimalFemaleGene ExpressionHumansLymphocytes, Tumor-InfiltratingMiceNeoplasmsProtein BindingRadiopharmaceuticalsAntibodies, MonoclonalCopper RadioisotopesCTLA-4 AntigenOrganometallic CompoundsRadiopharmaceuticals

Identifiers

PMID25365349
PMCPMC4217715
OpenAlexW2064701590

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.