Repeatability of <sup>18</sup>F-FLT PET in a Multicenter Study of Patients with High-Grade Glioma.

Lodge, Martin A; Holdhoff, Matthias; Leal, Jeffrey P; Bag, Asim K; Nabors, L Burt; Mintz, Akiva; Lesser, Glenn J; Mankoff, David A et al. · J Nucl Med · 2017

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Abstract

Quantitative 3'-deoxy-3'-<sup>18</sup>F-fluorothymidine (<sup>18</sup>F-FLT) PET has potential as a noninvasive tumor biomarker for the objective assessment of response to treatment. To guide interpretation of these quantitative data, we evaluated the repeatability of <sup>18</sup>F-FLT PET as part of a multicenter trial involving patients with high-grade glioma. <b>Methods:</b><sup>18</sup>F-FLT PET was performed on 10 patients with recurrent high-grade glioma at 5 different institutions within the Adult Brain Tumor Consortium trial ABTC1101. Data were acquired according to a double baseline protocol in which PET examinations were repeated within 2 d of each other with no intervening treatment. On each of the 2 imaging days, dedicated brain PET was performed at 2 time points, 1 and 3 h after <sup>18</sup>F-FLT administration. Tumor SUVs and related parameters were measured at a central laboratory using various volumes of interest: isocontour at 30% of the maximum pixel (SUV<sub>mean_30%</sub>), gradient-based segmentation (SUV<sub>mean_gradient</sub>), the maximum pixel (SUV<sub>max</sub>), and a 1-mL sphere at the region of highest uptake (SUV<sub>peak</sub>). Repeatability coefficients (RCs) were calculated from the relative differences between corresponding SUV measurements obtained on the 2 d. <b>Results:</b> RCs for tumor SUVs were 22.5% (SUV<sub>mean_30%</sub>), 23.8% (SUV<sub>mean_gradient</sub>), 23.2% (SUV<sub>max</sub>), and 18.5% (SUV<sub>peak</sub>) at 1 h after injection. Corresponding data at 3 h were 22.4%, 25.0%, 27.3%, and 23.6%. Normalizing the tumor SUV data with reference to a background region improved repeatability, and the most stable parameter was the tumor-to-background ratio derived using SUV<sub>peak</sub> (RC, 16.5%). <b>Conclusion:</b> SUV quantification of <sup>18</sup>F-FLT uptake in glioma had an RC in the range of 18%-24% when imaging began 1 h after <sup>18</sup>F-FLT administration. The volume-of-interest methodology had a small but not negligible influence on repeatability, with the best performance obtained using SUV<sub>peak</sub> Although changes in <sup>18</sup>F-FLT SUV after treatment cannot be directly interpreted as a change in tumor proliferation, we have established ranges beyond which SUV differences are likely due to legitimate biologic effects.

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