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.
