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


METHODS
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.
Ullrich
Roland
R
Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch-Laboratories, Cologne, Germany.
Backes
Heiko
H
Li
Hongfeng
H
Kracht
Lutz
L
Miletic
Hrvoje
H
Kesper
Kristina
K
Neumaier
Bernd
B
Heiss
Wolf-Dieter
WD
Wienhard
Klaus
K
Jacobs
Andreas H
AH
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D049109:Cell Proliferation; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008715:Methionine / Q000493:pharmacokinetics; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D015224:Dideoxynucleosides; D005462:Fluorine Radioisotopes; D019394:Ki-67 Antigen; D019275:Radiopharmaceuticals; D008715:Methionine; C002854:alovudine