Evidence map›Paper›PMID 23344138›Full record

ArticleEuropean journal of nuclear medicine and molecular imaging2013

PET imaging of CD105/endoglin expression with a ⁶¹/⁶⁴Cu-labeled Fab antibody fragment.

Yin Zhang, Hao Hong, Hakan Orbay, Hector F Valdovinos, Tapas R Nayak, Charles P Theuer, Todd E Barnhart, Weibo Cai

Open access · greenAbstract read
In one paragraph

Article in European journal of nuclear medicine and molecular imaging, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 2 pooled it
4.8field-weighted citation impact, top 5% 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

30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. Review
  7. Nanobodies as non-invasive imaging tools.Immuno-oncology technology · 2020
    Review
  8. Review
  9. Antibody-Based Tracers for PET/SPECT Imaging of Chronic Inflammatory Diseases.Chembiochem : a European journal of chemical biology · 2019
    Review
  10. Technology in cancer research & treatment · 2019
    Review
  11. Article
  12. ImmunoPET imaging of CD38 in murine lymphoma models usingEuropean journal of nuclear medicine and molecular imaging · 2018
    Article
  13. Targeting angiogenesis for radioimmunotherapy with aEuropean journal of nuclear medicine and molecular imaging · 2018
    Article
  14. Review
  15. Dual Targeting of Tissue Factor and CD105 for Preclinical PET Imaging of Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016
    Article
  16. Article
  17. Noninvasive brain cancer imaging with a bispecific antibody fragment, generated via click chemistry.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  18. Article
  19. PET Imaging of Abdominal Aortic Aneurysm with 64Cu-Labeled Anti-CD105 Antibody Fab Fragment.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2015
    Article
  20. 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

8 authors at 2 institutions in 1 country.

Yin ZhangDepartment of Medical Physics, University of Wisconsin - Madison, 1111 Highland Avenue, Madison, WI 53705-2275, USA.
Hao Hong
Hakan Orbay
Hector F Valdovinos
Tapas R Nayak
Charles P Theuer
Todd E Barnhart
Weibo Cai
University of Wisconsin–Madison · USTracon Pharmaceuticals (United States) · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
NCI NIH HHS P30 CA014520
6 · The paper itself

Abstract

purposeThe goal of this study was to generate and characterize the Fab fragment of TRC105, a monoclonal antibody that binds with high affinity to human and murine CD105 (i.e., endoglin), and investigate its potential for PET imaging of tumor angiogenesis in a small-animal model after (61/64)Cu labeling.

methodsTRC105-Fab was generated by enzymatic papain digestion. The integrity and CD105 binding affinity of TRC105-Fab was evaluated before NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) conjugation and (61/64)Cu labeling. Serial PET imaging and biodistribution studies were carried out in the syngeneic 4T1 murine breast cancer model to quantify tumor targeting efficiency and normal organ distribution of (61/64)Cu-NOTA-TRC105-Fab. Blocking studies with unlabeled TRC105 were performed to confirm CD105 specificity of the tracer in vivo. Immunofluorescence staining was also conducted to correlate tracer uptake in the tumor and normal tissues with CD105 expression.

resultsTRC105-Fab was produced with high purity through papain digestion of TRC105, as confirmed by SDS-PAGE, HPLC analysis, and mass spectrometry. (61/64)Cu labeling of NOTA-TRC105-Fab was achieved with about 50 % yield (specific activity about 44 GBq/μmol). PET imaging revealed rapid uptake of (64)Cu-NOTA-TRC105-Fab in the 4T1 tumor (3.6 ± 0.4, 4.2 ± 0.5, 4.9 ± 0.3, 4.4 ± 0.7, and 4.6 ± 0.8 %ID/g at 0.5, 2, 5, 16, and 24 h after injection, respectively; n = 4). Since tumor uptake peaked soon after tracer injection, (61)Cu-labeled TRC105-Fab was also able to provide tumor contrast at 3 and 8 h after injection. CD105 specificity of the tracer was confirmed with blocking studies and histological examination.

conclusionWe report PET imaging of CD105 expression using (61/64)Cu-NOTA-TRC105-Fab, which exhibited prominent and target-specific uptake in the 4T1 tumor. The use of a Fab fragment led to much faster tumor uptake (which peaked at a few hours after tracer injection) compared to radiolabeled intact antibody, which may be translated into same-day immunoPET imaging for clinical investigation.

Indexed as

Copper RadioisotopesGene Expression RegulationImmunoglobulin Fab FragmentsAnimalsAntibodies, MonoclonalAntigens, CDEndoglinFemaleHumansIsotope LabelingMammary Neoplasms, ExperimentalMCF-7 CellsMiceNeovascularization, PathologicPositron-Emission TomographyRadiometryAntibodies, MonoclonalAntigens, CDcarotuximabCopper RadioisotopesEndoglinENG protein, humanImmunoglobulin Fab FragmentsReceptors, Cell Surface

Identifiers

PMID23344138
PMCPMC3625465
OpenAlexW2059872450

What OpenQuestion holds

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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.