Early Detection of Erlotinib Treatment Response in NSCLC by 3′-Deoxy-3′-[\(^{18}F\)]-Fluoro-L-Thymidine ([\(^{18}F\)]FLT) Positron Emission Tomography (PET)

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Early Detection of Erlotinib Treatment Response in NSCLC by 3′-Deoxy-3′-[\(^{18}F\)]-Fluoro-L-Thymidine ([\(^{18}F\)]FLT) Positron Emission Tomography (PET)

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Title: Early Detection of Erlotinib Treatment Response in NSCLC by 3′-Deoxy-3′-[\(^{18}F\)]-Fluoro-L-Thymidine ([\(^{18}F\)]FLT) Positron Emission Tomography (PET)
Author: Ullrich, Roland T.; Zander, Thomas; Neumaier, Bernd; Koker, Mirjam; Waerzeggers, Yannic; Borgman, Christa L.; Tawadros, Samir; Li, Hongfeng; Sos, Martin L.; Backes, Heiko; Wolf, Jürgen; Jacobs, Andreas H.; Thomas, Roman K.; Winkeler, Alexandra; Shimamura, Takeshi; Shapiro, Geoffrey Ira

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Citation: Ullrich, Roland T., Thomas Zander, Bernd Neumaier, Mirjam Koker, Takeshi Shimamura, Yannic Waerzeggers, Christa L. Borgman, et al. 2008. Early detection of erlotinib treatment response in NSCLC by 3′-Deoxy-3′-[\(^{18}F\)]-Fluoro-L-Thymidine ([\(^{18}F\)]FLT) positron emission tomography (PET). PLoS ONE 3(12): e3908.
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Abstract: Background: Inhibition of the epidermal growth factor receptor (EGFR) has shown clinical success in patients with advanced non-small cell lung cancer (NSCLC). Somatic mutations of EGFR were found in lung adenocarcinoma that lead to exquisite dependency on EGFR signaling; thus patients with EGFR-mutant tumors are at high chance of response to EGFR inhibitors. However, imaging approaches affording early identification of tumor response in EGFR-dependent carcinomas have so far been lacking. Methodology/Principal Findings: We performed a systematic comparison of 3′-Deoxy-3′-[\(^{18}F\)]-fluoro-L-thymidine ([\(^{18}F\)]FLT) and 2-[\(^{18}F\)]-fluoro-2-deoxy-D-glucose ([\(^{18}F\)]FDG) positron emission tomography (PET) for their potential to identify response to EGFR inhibitors in a model of EGFR-dependent lung cancer early after treatment initiation. While erlotinib-sensitive tumors exhibited a striking and reproducible decrease in [\(^{18}F\)]FLT uptake after only two days of treatment, [\(^{18}F\)]FDG PET based imaging revealed no consistent reduction in tumor glucose uptake. In sensitive tumors, a decrease in [\(^{18}F\)]FLT PET but not [\(^{18}F\)]FDG PET uptake correlated with cell cycle arrest and induction of apoptosis. The reduction in [\(^{18}F\)]FLT PET signal at day 2 translated into dramatic tumor shrinkage four days later. Furthermore, the specificity of our results is confirmed by the complete lack of [\(^{18}F\)]FLT PET response of tumors expressing the T790M erlotinib resistance mutation of EGFR. Conclusions: [\(^{18}F\)]FLT PET enables robust identification of erlotinib response in EGFR-dependent tumors at a very early stage. [\(^{18}F\)]FLT PET imaging may represent an appropriate method for early prediction of response to EGFR TKI treatment in patients with NSCLC.
Published Version: doi://10.1371/journal.pone.0003908
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592703/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10198625
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