Glioma proliferation as assessed by 3′-fluoro-3′-deoxy-L-thymidine positron emission tomography in patients with newly diagnosed high-grade glioma

Purpose: The aim of this study was to investigate the relationship between the in vivo derived kinetic parameters of 3'-deoxy-3'-F-18-fluorothymicline (F-18-FLT) and the proliferation rate measured in vitro by Ki-67 staining in patients with newly diagnosed high-grade gliomas. Experimental Design: Thirteen patients with newly diagnosed high-grade gliomas were investigated with F-18-FLT and methyl-C-11-L-methionine (C-11-MET) positron emission tomography (PET) and T1-, Gd-T1-, and T2-weighted magnetic resonance imaging on consecutive days. Tracer kinetic parameters of F-18-FLT as well as the standardized uptake value and the tumor-to-background (T/B) ratio of F-18-FLT and C-11-MET were determined. Data of kinetic modeling, standardized uptake value, and T/B values derived from F-18-FLT-PET were compared with T/B values derived from C-11-MET-PET and to the in vitro proliferation marker Ki-67. Results: A significant correlation was observed between the metabolic rate constant Ki and the proliferation index as measured by Ki-67 immunostaining [Ki, r = 0.79 (P = 0.004)]. Also, the phosphorylation rate constant Q correlated with Ki-67 [k3, r = 0.76 (P = 0.006)], whereas the rate constant for transport through the blood brain barrier K1 showed a weaker correlation with Ki-67 [K1, r = 0.62 (P = 0.044)]. No significant correlation between C-11-MET and F-18-FLT uptake ratios and Ki-67 was observed. Conclusions: This study shows that kinetic analysis of F-18-FLT tracer uptake is essential for the in vivo assessment of tumor proliferation in high-grade gliomas, whereas uptake ratios of C-11-MET and F-18-FLT failed to correlate with the in vitro determined proliferation marker. Thus, kinetic analysis of F-18-FLT might provide an accurate method for the assessment of early response to glioma treatment in the future.