Figure 6.

Multitracer positron emission tomography (PET) evaluation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. ¹⁸F-3′-deoxy-3′-fluorothymidine (FLT) PET indicates response to therapy after 2 days of erlotinib treatment (50 mg kg^–1) in the EGFR TKI-sensitive non-small cell lung cancer xenografts PC9 (n=8; vehicle, n=2) and HCC827 (n=7; vehicle, n=2) (a). The PET signal remains reduced also after 4 days of erlotinib treatment. No significant decrease in ¹⁸F-FLT uptake was observed in the EGFR TKI-resistant H1975 xenografts (n=8; vehicle, n=2). Statistical analysis revealed a significant reduction in ¹⁸F-FLT uptake in HCC827 and PC9 xenografts (b) and no significant changes in the H1975 xenografts during therapy. ¹⁸F-FDG metabolism only slightly decreased after 4 days of erlotinib treatment in the HCC827 xenografts. However, even after 4 days of erlotinib treatment the reduction in ¹⁸F-FDG uptake was not significant. The decrease in ¹⁸F-FLT uptake was accompanied by inhibition of cell growth as assessed by Ki-67 staining (c). The strong correlation between ¹⁸F-FLT uptake and the in vitro proliferation marker Ki-67 highlights the ability of ¹⁸F-FLT to assess cell proliferation in vivo (r=0.87, p<0.001). In contrast, the correlation of Ki-67 expression to ¹⁸F-FDG uptake was much lower (r=0.38, p=0.0037) (d) (modified from Ullrich et al 2008 with permission [82]).