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

Roland Ullrich, Heiko Backes, Hongfeng Li, Lutz Kracht, Hrvoje Miletic, Kristina Kesper, Bernd Neumaier, Wolf-Dieter Heiss, Klaus Wienhard, Andreas H Jacobs
Clinical Cancer Research 2008 April 1, 14 (7): 2049-55

PURPOSE: The aim of this study was to investigate the relationship between the in vivo derived kinetic parameters of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-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 (18)F-FLT and methyl-(11)C- l-methionine ((11)C-MET) positron emission tomography (PET) and T1-, Gd-T1-, and T2-weighted magnetic resonance imaging on consecutive days. Tracer kinetic parameters of (18)F-FLT as well as the standardized uptake value and the tumor-to-background (T/B) ratio of (18)F-FLT and (11)C-MET were determined. Data of kinetic modeling, standardized uptake value, and T/B values derived from (18)F-FLT-PET were compared with T/B values derived from (11)C-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 k3 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 (11)C-MET and (18)F-FLT uptake ratios and Ki-67 was observed.

CONCLUSIONS: This study shows that kinetic analysis of (18)F-FLT tracer uptake is essential for the in vivo assessment of tumor proliferation in high-grade gliomas, whereas uptake ratios of (11)C-MET and (18)F-FLT failed to correlate with the in vitro determined proliferation marker. Thus, kinetic analysis of (18)F-FLT might provide an accurate method for the assessment of early response to glioma treatment in the future.

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