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18F-FLT    and 18F-FDOPA PET kinetics in recurrent brain tumors

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

In this study, kinetic parameters of the cellular proliferation tracer 18F-3′-deoxy-3′-fluoro-l-thymidine (FLT) and the amino acid probe 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (FDOPA) were measured before and early after the start of therapy, and were used to predict the overall survival (OS) of patients with recurrent malignant glioma using multiple linear regression (MLR) analysis.

Methods

High-grade recurrent brain tumors in 21 patients (11 men and 10 women, age range 26 – 76 years) were investigated. Each patient had three dynamic PET studies with each probe: at baseline and after 2 and 6 weeks from the start of treatment. Treatment consisted of biweekly cycles of bevacizumab (an angiogenesis inhibitor) and irinotecan (a chemotherapeutic agent). For each study, about 3.5 mCi of FLT (or FDOPA) was administered intravenously and dynamic PET images were acquired for 1 h (or 35 min for FDOPA). A total of 126 PET scans were analyzed. A three-compartment, two-tissue model was applied to estimate tumor FLT and FDOPA kinetic rate constants using a metabolite- and partial volume-corrected input function. MLR analysis was used to model OS as a function of FLT and FDOPA kinetic parameters for each of the three studies as well as their relative changes between studies. An exhaustive search of MLR models using three or fewer predictor variables was performed to find the best models.

Results

Kinetic parameters from FLT were more predictive of OS than those from FDOPA. The three-predictor MLR model derived using information from both probes (adjusted R 2 = 0.83) fitted the OS data better than that derived using information from FDOPA alone (adjusted R 2 = 0.41), but was only marginally different from that derived using information from FLT alone (adjusted R 2 = 0.82). Standardized uptake values (either from FLT alone, FDOPA alone, or both together) gave inferior predictive results (best adjusted R 2 = 0.25).

Conclusion

For recurrent malignant glioma treated with bevacizumab and irinotecan, FLT kinetic parameters obtained early after the start of treatment (absolute values and their associated changes) can provide sufficient information to predict OS with reasonable confidence using MLR. The slight increase in accuracy for predicting OS with a combination of FLT and FDOPA PET information may not warrant the additional acquisition of FDOPA PET for therapy monitoring in patients with recurrent glioma.

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Acknowledgments

The authors are grateful to all the patients who participated in this study as well as to their families. In addition, the authors thank David Truong, Dat Vu, and Weber Shao for their computer and database support, the UCLA Cyclotron staff for help with FLT and FDOPA preparation, and the UCLA Nuclear Medicine staff for acquisition of the PET scans. This work was supported by the US Department of Energy contract DEFG02-06ER64249 and NIH grants P50-CA086306 and R01-EB001943.

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Authors and Affiliations

  1. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, 90095-6948, USA

    Mirwais Wardak, Christiaan Schiepers, Magnus Dahlbom, Michael E. Phelps & Sung-Cheng Huang

  2. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Timothy F. Cloughesy

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  1. Mirwais Wardak
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  2. Christiaan Schiepers
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Correspondence to Sung-Cheng Huang.

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Wardak, M., Schiepers, C., Cloughesy, T.F. et al. 18F-FLT    and 18F-FDOPA PET kinetics in recurrent brain tumors. Eur J Nucl Med Mol Imaging 41, 1199–1209 (2014). https://doi.org/10.1007/s00259-013-2678-2

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