Evidence map›Paper›PMID 22214377›Full record

ArticleEJNMMI research2011

Failure of annexin-based apoptosis imaging in the assessment of antiangiogenic therapy effects.

Wiltrud Lederle, Susanne Arns, Anne Rix, Felix Gremse, Dennis Doleschel, Jörn Schmaljohann, Felix M Mottaghy, Fabian Kiessling, Moritz Palmowski

Open access · goldAbstract read
In one paragraph

Article in EJNMMI research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

24 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Detecting vascular normalization in epithelial ovarian cancer.Medical oncology (Northwood, London, England) · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Hybrid µCT-FMT imaging and image analysis.Journal of visualized experiments : JoVE · 2015
    Article
  14. Radiopharmaceuticals as probes to characterize tumour tissue.European journal of nuclear medicine and molecular imaging · 2015
    Review
  15. Article
  16. Article
  17. Article
  18. Bis(zinc-dipicolylamine), Zn-DPA, a new marker for apoptosis.Investigative ophthalmology & visual science · 2014
    Article
  19. 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

9 authors at 2 institutions in 2 countries.

Wiltrud LederleExperimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Pauwelsstraße 20, Aachen, 52074, Germany. wlederle@ukaachen.de.
Susanne Arns
Anne Rix
Felix Gremse
Dennis Doleschel
Jörn Schmaljohann
Felix M Mottaghy
Fabian Kiessling
Moritz Palmowski
RWTH Aachen University · DEMaastricht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMolecular apoptosis imaging is frequently discussed to be useful for monitoring cancer therapy. We demonstrate that the sole assessment of therapy effects by apoptosis imaging can be misleading, depending on the therapy effect on the tumor vasculature.

methodsApoptosis was investigated by determining the uptake of Annexin Vivo by optical imaging (study part I) and of 99 mTc-6-hydrazinonicotinic [HYNIC]-radiolabeled Annexin V by gamma counting (study part II) in subcutaneous epidermoid carcinoma xenografts (A431) in nude mice after antiangiogenic treatment (SU11248). Optical imaging was performed by optical tomography (3D) and 2D reflectance imaging (control, n = 7; therapy, n = 6). Accumulation of the radioactive tracer was determined ex vivo (control, n = 5; therapy, n = 6). Tumor vascularization was investigated with an optical blood pool marker (study part I) and contrast-enhanced ultrasound (both studies). Data were validated by immunohistology.

resultsA significantly higher apoptosis rate was detected in treated tumors by immunohistological terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining (area fraction: control, 0.023 ± 0.015%; therapy, 0.387 ± 0.105%; P < 0.001). However, both 2D reflectance imaging using Annexin Vivo (control, 13 ± 15 FI/cm2; therapy, 11 ± 7 FI/cm2) and gamma counting using 99 mTc-HYNIC-Annexin V (tumor-to-muscle ratio control, 5.66 ± 1.46; therapy, 6.09 ± 1.40) failed in showing higher accumulation in treated tumors. Optical tomography even indicated higher probe accumulation in controls (control, 81.3 ± 73.7 pmol/cm3; therapy, 27.5 ± 34.7 pmol/cm3). Vascularization was strongly reduced after therapy, demonstrated by contrast-enhanced ultrasound, optical imaging, and immunohistology.

conclusionsThe failure of annexin-based apoptosis assessment in vivo can be explained by the significant breakdown of the vasculature after therapy, resulting in reduced probe/tracer delivery. This favors annexin-based apoptosis imaging only in therapies that do not severely interfere with the vasculature.

Identifiers

PMID22214377
PMCPMC3251208
OpenAlexW2163149168

What OpenQuestion holds

Textmetadata
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.