Glioma proliferation as assessed by FLT-PET in patients with newly diagnosed high grade glioma

The aim of this study was to investigate the relationship between the in vivo derived kinetic parameters of 3((prime))-deoxy-3((prime))-18F-fluorothymidine (18F-FLT) and the proliferation rate measured in vitro by Ki-67 staining in patients with newly diagnosed high-grade gliomas.

Thirteen patients with newly diagnosed high grade gliomas were investigated with 18F-FLT and methyl-11C-L-methionine (11C-MET) positron emission tomography (PET) and T1-, Gd-T1 and T2-weighted MRI on consecutive days. Tracer kinetic parameters of 18F-FLT as well as the standardized uptake value (SUV) and the tumor-to-background (T/B) ratio of 18F-FLT and 11C-MET were determined. Data of kinetic modeling, SUV and T/B values derived from 18F-FLT-PET were compared to T/B values derived from 11C-MET-PET and to the in vitro proliferation marker Ki-67.

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)] while the rate constant for transport through the blood brain barrier (BBB) K1 showed a weaker correlation with Ki-67 [K1: r=0.62 (p=0.044)]. No significant correlation between 11C-MET and 18F-FLT uptake ratios and Ki-67 was observed.

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