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Title: A Comparative Study of the Hypoxia PET Tracers [{sup 18}F]HX4, [{sup 18}F]FAZA, and [{sup 18}F]FMISO in a Preclinical Tumor Model

Abstract

Purpose: Several individual clinical and preclinical studies have shown the possibility of evaluating tumor hypoxia by using noninvasive positron emission tomography (PET). The current study compared 3 hypoxia PET tracers frequently used in the clinic, [{sup 18}F]FMISO, [{sup 18}F]FAZA, and [{sup 18}F]HX4, in a preclinical tumor model. Tracer uptake was evaluated for the optimal time point for imaging, tumor-to-blood ratios (TBR), spatial reproducibility, and sensitivity to oxygen modification. Methods and Materials: PET/computed tomography (CT) images of rhabdomyosarcoma R1-bearing WAG/Rij rats were acquired at multiple time points post injection (p.i.) with one of the hypoxia tracers. TBR values were calculated, and reproducibility was investigated by voxel-to-voxel analysis, represented as correlation coefficients (R) or Dice similarity coefficient of the high-uptake volume. Tumor oxygen modifications were induced by exposure to either carbogen/nicotinamide treatment or 7% oxygen breathing. Results: TBR was stabilized and maximal at 2 hours p.i. for [{sup 18}F]FAZA (4.0 ± 0.5) and at 3 hours p.i. for [{sup 18}F]HX4 (7.2 ± 0.7), whereas [{sup 18}F]FMISO showed a constant increasing TBR (9.0 ± 0.8 at 6 hours p.i.). High spatial reproducibility was observed by voxel-to-voxel comparisons and Dice similarity coefficient calculations on the 30% highest uptake volume for both [{sup 18}F]FMISO (Rmore » = 0.86; Dice coefficient = 0.76) and [{sup 18}F]HX4 (R = 0.76; Dice coefficient = 0.70), whereas [{sup 18}F]FAZA was less reproducible (R = 0.52; Dice coefficient = 0.49). Modifying the hypoxic fraction resulted in enhanced mean standardized uptake values for both [{sup 18}F]HX4 and [{sup 18}F]FAZA upon 7% oxygen breathing. Only [{sup 18}F]FMISO uptake was found to be reversible upon exposure to nicotinamide and carbogen. Conclusions: This study indicates that each tracer has its own strengths and, depending on the question to be answered, a different tracer can be put forward.« less

Authors:
; ;  [1]; ; ;  [1]
  1. Department of Radiation Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands)
Publication Date:
OSTI Identifier:
22458602
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 91; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANOXIA; BIOMEDICAL RADIOGRAPHY; BLOOD; CAT SCANNING; COMPARATIVE EVALUATIONS; CORRELATIONS; FLUORINE 18; INJECTION; MODIFICATIONS; NEOPLASMS; NICOTINAMIDE; OXYGEN; POSITRON COMPUTED TOMOGRAPHY; RESPIRATION; SENSITIVITY; UPTAKE

Citation Formats

Peeters, Sarah G.J.A., E-mail: sarah.peeters@maastrichtuniversity.nl, Zegers, Catharina M.L., Lieuwes, Natasja G., Elmpt, Wouter van, Eriksson, Jonas, Dongen, Guus A.M.S. van, Dubois, Ludwig, and Lambin, Philippe. A Comparative Study of the Hypoxia PET Tracers [{sup 18}F]HX4, [{sup 18}F]FAZA, and [{sup 18}F]FMISO in a Preclinical Tumor Model. United States: N. p., 2015. Web. doi:10.1016/J.IJROBP.2014.09.045.
Peeters, Sarah G.J.A., E-mail: sarah.peeters@maastrichtuniversity.nl, Zegers, Catharina M.L., Lieuwes, Natasja G., Elmpt, Wouter van, Eriksson, Jonas, Dongen, Guus A.M.S. van, Dubois, Ludwig, & Lambin, Philippe. A Comparative Study of the Hypoxia PET Tracers [{sup 18}F]HX4, [{sup 18}F]FAZA, and [{sup 18}F]FMISO in a Preclinical Tumor Model. United States. https://doi.org/10.1016/J.IJROBP.2014.09.045
Peeters, Sarah G.J.A., E-mail: sarah.peeters@maastrichtuniversity.nl, Zegers, Catharina M.L., Lieuwes, Natasja G., Elmpt, Wouter van, Eriksson, Jonas, Dongen, Guus A.M.S. van, Dubois, Ludwig, and Lambin, Philippe. 2015. "A Comparative Study of the Hypoxia PET Tracers [{sup 18}F]HX4, [{sup 18}F]FAZA, and [{sup 18}F]FMISO in a Preclinical Tumor Model". United States. https://doi.org/10.1016/J.IJROBP.2014.09.045.
@article{osti_22458602,
title = {A Comparative Study of the Hypoxia PET Tracers [{sup 18}F]HX4, [{sup 18}F]FAZA, and [{sup 18}F]FMISO in a Preclinical Tumor Model},
author = {Peeters, Sarah G.J.A., E-mail: sarah.peeters@maastrichtuniversity.nl and Zegers, Catharina M.L. and Lieuwes, Natasja G. and Elmpt, Wouter van and Eriksson, Jonas and Dongen, Guus A.M.S. van and Dubois, Ludwig and Lambin, Philippe},
abstractNote = {Purpose: Several individual clinical and preclinical studies have shown the possibility of evaluating tumor hypoxia by using noninvasive positron emission tomography (PET). The current study compared 3 hypoxia PET tracers frequently used in the clinic, [{sup 18}F]FMISO, [{sup 18}F]FAZA, and [{sup 18}F]HX4, in a preclinical tumor model. Tracer uptake was evaluated for the optimal time point for imaging, tumor-to-blood ratios (TBR), spatial reproducibility, and sensitivity to oxygen modification. Methods and Materials: PET/computed tomography (CT) images of rhabdomyosarcoma R1-bearing WAG/Rij rats were acquired at multiple time points post injection (p.i.) with one of the hypoxia tracers. TBR values were calculated, and reproducibility was investigated by voxel-to-voxel analysis, represented as correlation coefficients (R) or Dice similarity coefficient of the high-uptake volume. Tumor oxygen modifications were induced by exposure to either carbogen/nicotinamide treatment or 7% oxygen breathing. Results: TBR was stabilized and maximal at 2 hours p.i. for [{sup 18}F]FAZA (4.0 ± 0.5) and at 3 hours p.i. for [{sup 18}F]HX4 (7.2 ± 0.7), whereas [{sup 18}F]FMISO showed a constant increasing TBR (9.0 ± 0.8 at 6 hours p.i.). High spatial reproducibility was observed by voxel-to-voxel comparisons and Dice similarity coefficient calculations on the 30% highest uptake volume for both [{sup 18}F]FMISO (R = 0.86; Dice coefficient = 0.76) and [{sup 18}F]HX4 (R = 0.76; Dice coefficient = 0.70), whereas [{sup 18}F]FAZA was less reproducible (R = 0.52; Dice coefficient = 0.49). Modifying the hypoxic fraction resulted in enhanced mean standardized uptake values for both [{sup 18}F]HX4 and [{sup 18}F]FAZA upon 7% oxygen breathing. Only [{sup 18}F]FMISO uptake was found to be reversible upon exposure to nicotinamide and carbogen. Conclusions: This study indicates that each tracer has its own strengths and, depending on the question to be answered, a different tracer can be put forward.},
doi = {10.1016/J.IJROBP.2014.09.045},
url = {https://www.osti.gov/biblio/22458602}, journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 2,
volume = 91,
place = {United States},
year = {Sun Feb 01 00:00:00 EST 2015},
month = {Sun Feb 01 00:00:00 EST 2015}
}