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- W2578543847 abstract "1188 Objectives Non-small cell lung cancer (NSCLC) patients are treated with erlotinib, a tyrosine kinase inhibitor which targets the epidermal growth factor receptor (EGFR). Positron emission tomography (PET) imaging revealed higher uptake of [11C]erlotinib in tumors with activating EGFR mutations than in tumors with wild type EGFR [1,2]. Aim of this study was to measure the in vitro uptake of [11C]erlotinib in cancer cells. Methods Glioblastoma (U-87 MG) and NSCLC cells (erlotinib-sensitive HCC827, erlotinib-resistant HCC827, and gefitinib-resistant HCC827) were incubated with [11C]erlotinib up to 100 min or pretreated with unlabeled erlotinib or the Pgp/Bcrp inhibitor elacridar (both 1 µM) and then incubated with [11C]erlotinib for 30 min. Retained radioactivity in the cells was measured in a gamma counter and expressed as % injected dose (%ID). Results Uptake of [11C]erlotinib after 100 min was higher in erlotinib-sensitive HCC827 cells with an exon 19 deletion (1.72±0.19 %ID) and in gefitinib-resistant HCC827 cells (1.73±0.06 %ID) as compared with erlotinib-resistant HCC827 cells (0.97±0.04 %ID) and U-87 MG cells (0.38±0.03 %ID). [11C]Erlotinib uptake continued to rise in erlotinib-resistant HCC827 cells, whereas in all other cells it reached a plateau. In all HCC827 cells [11C]erlotinib uptake was significantly reduced following pretreatment with unlabeled erlotinib. Elacridar had no effect on [11C]erlotinib uptake in all cells. Conclusions We found distinct uptake kinetics and lower uptake of [11C]erlotinib in erlotinib-resistant HCC827 cells as compared with erlotinib-sensitive HCC827 cells. We also showed a significant reduction of [11C]erlotinib uptake in all NSCLC cells after pretreatment with unlabeled erlotinib suggesting specific binding to EGFR. Efflux by Pgp and Bcrp was not evident in the studied cells. Our results further support that [11C]erlotinib PET may be able to distinguish erlotinib-sensitive from erlotinib-resistant tumors. Research Support Lower Austria Corporation for Research and Education (NFB) project LF12-006 and Austrian Science Fund (FWF) project F 3513-B20." @default.
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- W2578543847 date "2015-05-01" @default.
- W2578543847 modified "2023-09-24" @default.
- W2578543847 title "In vitro uptake experiments in different cancer cell lines using [11C]erlotinib" @default.
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