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Glioma Proliferation as Assessed by 3‘-Fluoro-3’-Deoxy-L-Thymidine Positron Emission Tomography in Patients with Newly Diagnosed High-Grade Glioma

Authors' Affiliations: ¹ Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch-Laboratories; ² Center for Molecular Medicine, Departments of ³ Neurology and ⁴ Neuropathology at the University of Cologne; and ⁵ Klinikum Fulda, Germany

Requests for reprints: Andreas H. Jacobs, Laboratory for Gene Therapy and Molecular Imaging, Max-Planck-Institute for Neurological Research, Gleueler Street 50, 50931 Cologne, Germany. Phone: 49-221-4726-219; Fax: 49-221-4726-298; E-mail: Andreas.Jacobs{at}nf.mpg.de.

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

Conclusions: This study shows 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.