Repeatability of 18F-FLT PET in a multicenter study of patients with high-grade glioma

Martin Lodge, Matthias Holdhoff, Jeffrey Pettit Leal, Asim K. Bag, L. Burt Nabors, Akiva Mintz, Glenn J. Lesser, David A. Mankoff, Arati S. Desai, James M. Mountz, Frank S. Lieberman, Joy D. Fisher, Serena Desideri, Xiaobu Ye, Stuart A Grossman, David Schiff, Richard L. Wahl

Research output: Contribution to journalArticle

Abstract

Quantitative 39-deoxy-39-18F-fluorothymidine (18F-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 18F-FLT PET as part of a multicenter trial involving patients with high-grade glioma. Methods: 18F-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 18F-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 (SUVmean-30%), gradient-based segmentation (SUVmean-gradient), the maximum pixel (SUVmax), and a 1-mL sphere at the region of highest uptake (SUVpeak). Repeatability coefficients (RCs) were calculated fromthe relative differences between corresponding SUV measurements obtained on the 2 d. Results: RCs for tumor SUVs were 22.5% (SUVmean-30%), 23.8% (SUVmean-gradient), 23.2% (SUVmax), and 18.5% (SUVpeak) 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 SUVpeak (RC, 16.5%). Conclusion: SUV quantification of 18F-FLT uptake in glioma had an RC in the range of 18%- 24% when imaging began 1 h after 18F-FLT administration. The volume-of-interest methodology had a small but not negligible influence on repeatability, with the best performance obtained using SUVpeak. Although changes in 18F-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.

Original languageEnglish (US)
Pages (from-to)393-398
Number of pages6
JournalJournal of Nuclear Medicine
Volume58
Issue number3
DOIs
StatePublished - Mar 1 2017

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Glioma
Multicenter Studies
Neoplasms
Tumor Biomarkers
Brain Neoplasms
Therapeutics
Injections
Brain

Keywords

  • FLT
  • Glioma
  • PET
  • Repeatability
  • Reproducibility
  • SUV

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Repeatability of 18F-FLT PET in a multicenter study of patients with high-grade glioma. / Lodge, Martin; Holdhoff, Matthias; Leal, Jeffrey Pettit; Bag, Asim K.; Nabors, L. Burt; Mintz, Akiva; Lesser, Glenn J.; Mankoff, David A.; Desai, Arati S.; Mountz, James M.; Lieberman, Frank S.; Fisher, Joy D.; Desideri, Serena; Ye, Xiaobu; Grossman, Stuart A; Schiff, David; Wahl, Richard L.

In: Journal of Nuclear Medicine, Vol. 58, No. 3, 01.03.2017, p. 393-398.

Research output: Contribution to journalArticle

Lodge, M, Holdhoff, M, Leal, JP, Bag, AK, Nabors, LB, Mintz, A, Lesser, GJ, Mankoff, DA, Desai, AS, Mountz, JM, Lieberman, FS, Fisher, JD, Desideri, S, Ye, X, Grossman, SA, Schiff, D & Wahl, RL 2017, 'Repeatability of 18F-FLT PET in a multicenter study of patients with high-grade glioma', Journal of Nuclear Medicine, vol. 58, no. 3, pp. 393-398. https://doi.org/10.2967/jnumed.116.178434
Lodge, Martin ; Holdhoff, Matthias ; Leal, Jeffrey Pettit ; Bag, Asim K. ; Nabors, L. Burt ; Mintz, Akiva ; Lesser, Glenn J. ; Mankoff, David A. ; Desai, Arati S. ; Mountz, James M. ; Lieberman, Frank S. ; Fisher, Joy D. ; Desideri, Serena ; Ye, Xiaobu ; Grossman, Stuart A ; Schiff, David ; Wahl, Richard L. / Repeatability of 18F-FLT PET in a multicenter study of patients with high-grade glioma. In: Journal of Nuclear Medicine. 2017 ; Vol. 58, No. 3. pp. 393-398.
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abstract = "Quantitative 39-deoxy-39-18F-fluorothymidine (18F-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 18F-FLT PET as part of a multicenter trial involving patients with high-grade glioma. Methods: 18F-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 18F-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 (SUVmean-30{\%}), gradient-based segmentation (SUVmean-gradient), the maximum pixel (SUVmax), and a 1-mL sphere at the region of highest uptake (SUVpeak). Repeatability coefficients (RCs) were calculated fromthe relative differences between corresponding SUV measurements obtained on the 2 d. Results: RCs for tumor SUVs were 22.5{\%} (SUVmean-30{\%}), 23.8{\%} (SUVmean-gradient), 23.2{\%} (SUVmax), and 18.5{\%} (SUVpeak) 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 SUVpeak (RC, 16.5{\%}). Conclusion: SUV quantification of 18F-FLT uptake in glioma had an RC in the range of 18{\%}- 24{\%} when imaging began 1 h after 18F-FLT administration. The volume-of-interest methodology had a small but not negligible influence on repeatability, with the best performance obtained using SUVpeak. Although changes in 18F-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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T1 - Repeatability of 18F-FLT PET in a multicenter study of patients with high-grade glioma

AU - Lodge, Martin

AU - Holdhoff, Matthias

AU - Leal, Jeffrey Pettit

AU - Bag, Asim K.

AU - Nabors, L. Burt

AU - Mintz, Akiva

AU - Lesser, Glenn J.

AU - Mankoff, David A.

AU - Desai, Arati S.

AU - Mountz, James M.

AU - Lieberman, Frank S.

AU - Fisher, Joy D.

AU - Desideri, Serena

AU - Ye, Xiaobu

AU - Grossman, Stuart A

AU - Schiff, David

AU - Wahl, Richard L.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Quantitative 39-deoxy-39-18F-fluorothymidine (18F-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 18F-FLT PET as part of a multicenter trial involving patients with high-grade glioma. Methods: 18F-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 18F-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 (SUVmean-30%), gradient-based segmentation (SUVmean-gradient), the maximum pixel (SUVmax), and a 1-mL sphere at the region of highest uptake (SUVpeak). Repeatability coefficients (RCs) were calculated fromthe relative differences between corresponding SUV measurements obtained on the 2 d. Results: RCs for tumor SUVs were 22.5% (SUVmean-30%), 23.8% (SUVmean-gradient), 23.2% (SUVmax), and 18.5% (SUVpeak) 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 SUVpeak (RC, 16.5%). Conclusion: SUV quantification of 18F-FLT uptake in glioma had an RC in the range of 18%- 24% when imaging began 1 h after 18F-FLT administration. The volume-of-interest methodology had a small but not negligible influence on repeatability, with the best performance obtained using SUVpeak. Although changes in 18F-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.

AB - Quantitative 39-deoxy-39-18F-fluorothymidine (18F-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 18F-FLT PET as part of a multicenter trial involving patients with high-grade glioma. Methods: 18F-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 18F-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 (SUVmean-30%), gradient-based segmentation (SUVmean-gradient), the maximum pixel (SUVmax), and a 1-mL sphere at the region of highest uptake (SUVpeak). Repeatability coefficients (RCs) were calculated fromthe relative differences between corresponding SUV measurements obtained on the 2 d. Results: RCs for tumor SUVs were 22.5% (SUVmean-30%), 23.8% (SUVmean-gradient), 23.2% (SUVmax), and 18.5% (SUVpeak) 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 SUVpeak (RC, 16.5%). Conclusion: SUV quantification of 18F-FLT uptake in glioma had an RC in the range of 18%- 24% when imaging began 1 h after 18F-FLT administration. The volume-of-interest methodology had a small but not negligible influence on repeatability, with the best performance obtained using SUVpeak. Although changes in 18F-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.

KW - FLT

KW - Glioma

KW - PET

KW - Repeatability

KW - Reproducibility

KW - SUV

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