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Imaging Proliferation in Brain Tumors with ¹⁸F-FLT PET: Comparison with ¹⁸F-FDG

¹ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California
² Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, California
³ Department of Neurosurgery, David Geffen School of Medicine, UCLA, Los Angeles, California
⁴ Department of Pathology, David Geffen School of Medicine, UCLA, Los Angeles, California

3'-Deoxy-3'-¹⁸F-fluorothymidine (¹⁸F-FLT) is a recently developed PET tracer to image tumor cell proliferation. We characterized ¹⁸F-FLT PET of brain gliomas and compared ¹⁸F-FLT with ¹⁸F-FDG PET in side-by-side studies of the same patients. Methods: Twenty-five patients with newly diagnosed or previously treated glioma underwent PET with ¹⁸F-FLT and ¹⁸F-FDG on consecutive days. Three stable patients in long-term remission were included as negative control subjects. Tracer kinetics in normal brain and tumor were measured. Uptake of ¹⁸F-FLT and ¹⁸F-FDG was quantified by the standardized uptake value (SUV) and the tumor-to-normal tissue (T/N) ratio. The accuracy of ¹⁸F-FLT and ¹⁸F-FDG PET in evaluating newly diagnosed and recurrent gliomas was compared. More than half of the patients underwent resection after the PET study and correlations between PET uptake and the Ki-67 proliferation index were examined. Patients were monitored for a mean of 15.4 mo (range, 12–20 mo). The predictive power of PET for tumor progression and survival was analyzed using Kaplan–Meier statistics. Results: ¹⁸F-FLT uptake in tumors was rapid, peaking at 5–10 min after injection and remaining stable up to 75 min. Hence, a 30-min scan beginning at 5 min after injection was sufficient for imaging. ¹⁸F-FLT visualized all high-grade (grade III or IV) tumors. Grade II tumor did not show appreciable ¹⁸F-FLT uptake and neither did the stable lesions. The absolute uptake of ¹⁸F-FLT was low (maximum-pixel SUV [SUV_max], 1.33) but image contrast was better than with ¹⁸F-FDG (T/N ratio, 3.85 vs. 1.49). ¹⁸F-FDG PET studies were negative in 5 patients with recurrent high-grade glioma who subsequently suffered tumor progression within 1–3 mo. ¹⁸F-FLT SUV_max correlated more strongly with Ki-67 index (r = 0.84; P < 0.0001) than ¹⁸F-FDG SUV_max (r = 0.51; P = 0.07). ¹⁸F-FLT uptake also had more significant predictive power with respect to tumor progression and survival (P = 0.0005 and P = 0.001, respectively). Conclusion: Thirty-minute ¹⁸F-FLT PET 5 min after injection was more sensitive than ¹⁸F-FDG to image recurrent high-grade tumors, correlated better with Ki-67 values, and was a more powerful predictor of tumor progression and survival. Thus, ¹⁸F-FLT appears to be a promising tracer as a surrogate marker of proliferation in high-grade gliomas.

Key Words: ¹⁸F-FLT • ¹⁸F-FDG • Ki-67 • proliferation • brain tumor

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