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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 6/2014

01-06-2014 | Original Article

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

Authors: Mirwais Wardak, Christiaan Schiepers, Timothy F. Cloughesy, Magnus Dahlbom, Michael E. Phelps, Sung-Cheng Huang

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2014

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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.
Appendix
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Metadata
Title
18F-FLT    and 18F-FDOPA PET kinetics in recurrent brain tumors
Authors
Mirwais Wardak
Christiaan Schiepers
Timothy F. Cloughesy
Magnus Dahlbom
Michael E. Phelps
Sung-Cheng Huang
Publication date
01-06-2014
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2014
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-013-2678-2

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