↓ Skip to main content

A comparative PET imaging study with the reversible and irreversible EGFR tyrosine kinase inhibitors [11C]erlotinib and [18F]afatinib in lung cancer-bearing mice

Overview of attention for article published in EJNMMI Research, March 2015
Altmetric Badge

About this Attention Score

  • Average Attention Score compared to outputs of the same age
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

twitter
2 X users
facebook
1 Facebook page

Citations

dimensions_citation
39 Dimensions

Readers on

mendeley
51 Mendeley
Title
A comparative PET imaging study with the reversible and irreversible EGFR tyrosine kinase inhibitors [11C]erlotinib and [18F]afatinib in lung cancer-bearing mice
Published in
EJNMMI Research, March 2015
DOI 10.1186/s13550-015-0088-0
Pubmed ID
Authors

Paul Slobbe, Albert D Windhorst, Marijke Stigter-van Walsum, Egbert F Smit, Heiko G Niessen, Flavio Solca, Gerd Stehle, Guus A M S van Dongen, Alex J Poot

Abstract

Tyrosine kinase inhibitors (TKIs) have experienced a tremendous boost in the last decade, where more than 15 small molecule TKIs have been approved by the FDA. Unfortunately, despite their promising clinical successes, a large portion of patients remain unresponsive to these targeted drugs. For non-small cell lung cancer (NSCLC), the effectiveness of TKIs is dependent on the mutational status of epidermal growth factor receptor (EGFR). The exon 19 deletion as well as the L858R point mutation lead to excellent sensitivity to TKIs such as erlotinib and gefitinib; however, despite initial good response, most patients invariably develop resistance against these first-generation reversible TKIs, e.g., via T790M point mutation. Second-generation TKIs that irreversibly bind to EGFR wild-type and mutant isoforms have therefore been developed and one of these candidates, afatinib, has now reached the market. Whether irreversible TKIs differ from reversible TKIs in their in vivo tumor-targeting properties is, however, not known and is the subject of the present study. Erlotinib was labeled with carbon-11 and afatinib with fluorine-18 without modifying the structure of these compounds. A preclinical positron emission tomography (PET) study was performed in mice bearing NSCLC xenografts with a representative panel of mutations: an EGFR-WT xenograft cell line (A549), an acquired treatment-resistant L858R/T790M mutant (H1975), and a treatment-sensitive exon 19 deleted mutant (HCC827). PET imaging was performed in these xenografts with both tracers. Additionally, the effect of drug efflux transporter permeability glycoprotein (P-gp) on the tumor uptake of tracers was explored by therapeutic blocking with tariquidar. Both tracers only demonstrated selective tumor uptake in the HCC827 xenograft line (tumor-to-background ratio, [(11)C]erlotinib 1.9 ± 0.5 and [(18)F]afatinib 2.3 ± 0.4), thereby showing the ability to distinguish sensitizing mutations in vivo. No major differences were observed in the kinetics of the reversible and the irreversible tracers in each of the xenograft models. Under P-gp blocking conditions, no significant changes in tumor-to-background ratio were observed; however, [(18)F]afatinib demonstrated better tumor retention in all xenograft models. TKI-PET provides a method to image sensitizing mutations and can be a valuable tool to compare the distinguished targeting properties of TKIs in vivo.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 51 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 29%
Researcher 10 20%
Professor 4 8%
Other 3 6%
Student > Master 3 6%
Other 6 12%
Unknown 10 20%
Readers by discipline Count As %
Medicine and Dentistry 14 27%
Agricultural and Biological Sciences 7 14%
Pharmacology, Toxicology and Pharmaceutical Science 5 10%
Chemistry 5 10%
Biochemistry, Genetics and Molecular Biology 3 6%
Other 3 6%
Unknown 14 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 April 2015.
All research outputs
#15,329,087
of 22,799,071 outputs
Outputs from EJNMMI Research
#253
of 556 outputs
Outputs of similar age
#156,695
of 262,953 outputs
Outputs of similar age from EJNMMI Research
#10
of 17 outputs
Altmetric has tracked 22,799,071 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 556 research outputs from this source. They receive a mean Attention Score of 2.5. This one is in the 44th percentile – i.e., 44% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 262,953 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.