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Evaluation of (99m)Tc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR-activating mutations in NSCLC

Tyrosine kinase inhibitors (EGFR-TKIs) targeting the epidermal growth factor receptor (EGFR) have been used in non-small cell lung carcinoma (NSCLC) for years with promising results, in particular in patients with activating mutations in the EGFR kinase domain (exon 19 E746-A750 deletion or exon 21...

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Autores principales: Xiao, Zunyu, Song, Yan, Kai, Wang, Sun, Xilin, Shen, Baozhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522229/
https://www.ncbi.nlm.nih.gov/pubmed/28489575
http://dx.doi.org/10.18632/oncotarget.17251
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author Xiao, Zunyu
Song, Yan
Kai, Wang
Sun, Xilin
Shen, Baozhong
author_facet Xiao, Zunyu
Song, Yan
Kai, Wang
Sun, Xilin
Shen, Baozhong
author_sort Xiao, Zunyu
collection PubMed
description Tyrosine kinase inhibitors (EGFR-TKIs) targeting the epidermal growth factor receptor (EGFR) have been used in non-small cell lung carcinoma (NSCLC) for years with promising results, in particular in patients with activating mutations in the EGFR kinase domain (exon 19 E746-A750 deletion or exon 21 L858R point mutation). However, despite their great success in the clinic, a significant number of patients do not respond to EGFR-TKIs, such as those carrying the L858R/T790M mutation or EGFR wild type. Thus, detecting the EGFR mutation status before EGFR-TKIs therapy is essential to ensure its efficacy. In this study, we report a novel SPECT tracer (99m)Tc-HYNIC-MPG that binds specifically to activating mutant EGFR and which could therefore be used to noninvasively select patients sensitive to EGFR-TKIs. We evaluated the capacity of (99m)Tc-HYNIC-MPG in detecting EGFR-activating mutations both in vitro and in vivo using four human NSCLC cell lines (PC9, H1975, H358 and H520). (99m)Tc-HYNIC-MPG had significantly higher accumulation in PC9 tumor cells when compared to H1975, H358 and H520 tumors cells, which may be due to the activating mutations (exon 19 deletion) in EGFR tyrosine kinase domain in PC9 cells. Thus, (99m)Tc-HYNIC-MPG SPECT imaging may be used to identify NSCLC tumors with a potential high response rate to EGFR-TKIs.
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spelling pubmed-55222292017-08-21 Evaluation of (99m)Tc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR-activating mutations in NSCLC Xiao, Zunyu Song, Yan Kai, Wang Sun, Xilin Shen, Baozhong Oncotarget Research Paper Tyrosine kinase inhibitors (EGFR-TKIs) targeting the epidermal growth factor receptor (EGFR) have been used in non-small cell lung carcinoma (NSCLC) for years with promising results, in particular in patients with activating mutations in the EGFR kinase domain (exon 19 E746-A750 deletion or exon 21 L858R point mutation). However, despite their great success in the clinic, a significant number of patients do not respond to EGFR-TKIs, such as those carrying the L858R/T790M mutation or EGFR wild type. Thus, detecting the EGFR mutation status before EGFR-TKIs therapy is essential to ensure its efficacy. In this study, we report a novel SPECT tracer (99m)Tc-HYNIC-MPG that binds specifically to activating mutant EGFR and which could therefore be used to noninvasively select patients sensitive to EGFR-TKIs. We evaluated the capacity of (99m)Tc-HYNIC-MPG in detecting EGFR-activating mutations both in vitro and in vivo using four human NSCLC cell lines (PC9, H1975, H358 and H520). (99m)Tc-HYNIC-MPG had significantly higher accumulation in PC9 tumor cells when compared to H1975, H358 and H520 tumors cells, which may be due to the activating mutations (exon 19 deletion) in EGFR tyrosine kinase domain in PC9 cells. Thus, (99m)Tc-HYNIC-MPG SPECT imaging may be used to identify NSCLC tumors with a potential high response rate to EGFR-TKIs. Impact Journals LLC 2017-04-19 /pmc/articles/PMC5522229/ /pubmed/28489575 http://dx.doi.org/10.18632/oncotarget.17251 Text en Copyright: © 2017 Xiao et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Xiao, Zunyu
Song, Yan
Kai, Wang
Sun, Xilin
Shen, Baozhong
Evaluation of (99m)Tc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR-activating mutations in NSCLC
title Evaluation of (99m)Tc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR-activating mutations in NSCLC
title_full Evaluation of (99m)Tc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR-activating mutations in NSCLC
title_fullStr Evaluation of (99m)Tc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR-activating mutations in NSCLC
title_full_unstemmed Evaluation of (99m)Tc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR-activating mutations in NSCLC
title_short Evaluation of (99m)Tc-HYNIC-MPG as a novel SPECT radiotracer to detect EGFR-activating mutations in NSCLC
title_sort evaluation of (99m)tc-hynic-mpg as a novel spect radiotracer to detect egfr-activating mutations in nsclc
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522229/
https://www.ncbi.nlm.nih.gov/pubmed/28489575
http://dx.doi.org/10.18632/oncotarget.17251
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