| Title |
Early 18F-FDG uptake as a reliable imaging biomarker of T790M-mediated resistance but not MET amplification in non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors
|
|---|---|
| Published in |
EJNMMI Research, October 2016
|
| DOI | 10.1186/s13550-016-0229-0 |
| Pubmed ID | |
| Authors |
Viviana De Rosa, Viviana De Rosa, Francesca Iommelli, Marcello Monti, Ciro Gabriele Mainolfi, Rosa Fonti, Silvana Del Vecchio |
| Abstract |
The two main mechanisms of resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) are the occurrence of T790M secondary mutation in the kinase domain of EGFR and MET amplification. The aim of the present study was to test whether early changes of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in animal models bearing erlotinib-resistant NSCLC may have different imaging patterns of response to erlotinib depending on the molecular mechanisms underlying resistance. Animal tumor models were developed using NSCLC H1975 cells bearing the T790M mutation and H1993 cells with MET amplification. Nude mice bearing erlotinib-resistant H1975 and H1993 xenografts (four animals for each cell line and for each treatment) were subjected to (18)F-FDG PET/CT scan before and immediately after treatment (50 mg/kg p.o. for 3 days) with erlotinib, WZ4002, crizotinib, or vehicle. A three-dimensional region of interest analysis was performed to determine the percent change of (18)F-FDG uptake in response to treatment. At the end of the imaging studies, tumors were removed and analyzed for glycolytic and mitochondrial proteins as well as levels of cyclin D1. Imaging studies with (18)F-FDG PET/CT in H1975 tumor-bearing mice showed a reduction of (18)F-FDG uptake of 25.87 % ± 8.93 % after treatment with WZ4002 whereas an increase of (18)F-FDG uptake up to 23.51 % ± 9.72 % was observed after treatment with erlotinib or vehicle. Conversely, H1993 tumors showed a reduction of (18)F-FDG uptake after treatment with both crizotinib (14.70 % ± 1.30 %) and erlotinib (18.40 % ± 9.19 %) and an increase of tracer uptake in vehicle-treated (56.65 % ± 5.65 %) animals. The in vivo reduction of (18)F-FDG uptake was always associated with downregulation of HKII and p-PKM2 Tyr105 glycolytic proteins and upregulation of mitochondrial complexes (subunits I-IV) in excised tumors. (18)F-FDG uptake is a reliable imaging biomarker of T790M-mediated resistance and its reversal in NSCLC whereas it may not be accurate in the detection of MET-mediated resistance. |
Mendeley readers
The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 16 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 3 | 19% |
| Student > Bachelor | 2 | 13% |
| Professor | 2 | 13% |
| Other | 1 | 6% |
| Student > Postgraduate | 1 | 6% |
| Other | 0 | 0% |
| Unknown | 7 | 44% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 31% |
| Biochemistry, Genetics and Molecular Biology | 1 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 6% |
| Nursing and Health Professions | 1 | 6% |
| Engineering | 1 | 6% |
| Other | 0 | 0% |
| Unknown | 7 | 44% |
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 15 October 2016.
All research outputs
#20,346,264
of 22,893,031 outputs
Outputs from EJNMMI Research
#387
of 558 outputs
Outputs of similar age
#277,086
of 320,105 outputs
Outputs of similar age from EJNMMI Research
#4
of 5 outputs
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