Ullrich, Roland T.Zander, ThomasNeumaier, BerndKoker, MirjamWaerzeggers, YannicBorgman, Christa L.Tawadros, SamirLi, HongfengSos, Martin L.Backes, HeikoWolf, JürgenJacobs, Andreas H.Thomas, Roman K.Winkeler, AlexandraShimamura, TakeshiShapiro, Geoffrey2013-01-182008Ullrich, 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): e3908.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10198625Background: 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.en-UScell biologycell signalingoncologylung cancermedical imagingradiologySPECT imagingPET imagingJournal Article2013-01-1810.1371/journal.pone.0003908