| Autor: |
Roland T Ullrich, Thomas Zander, Bernd Neumaier, Mirjam Koker, Takeshi Shimamura, Yannic Waerzeggers, Christa L Borgman, Samir Tawadros, Hongfeng Li, Martin L Sos, Heiko Backes, Geoffrey I Shapiro, Jürgen Wolf, Andreas H Jacobs, Roman K Thomas, Alexandra Winkeler |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| Předmět: |
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| Zdroj: |
PLoS ONE, Vol 3, Iss 12, p e3908 (2008) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0003908 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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