Superiority of 68Ga-DOTATATE over 18F-FDG and anatomic imaging in the detection of succinate dehydrogenase mutation (SDHx )-related pheochromocytoma and paraganglioma in the pediatric population
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To evaluate and compare diagnostic performance of 68Ga-DOTA(0)-Tyr(3)-octreotate (68Ga-DOTATATE) with 18F–fluoro-2-deoxy-D-glucose (18F–FDG) positron emission tomography-computed tomography (PET/CT) and anatomic imaging using computed tomography and/or magnetic resonance (CT/MR) imaging in detection of SDHx-related pheochromocytomas and paragangliomas (PPGLs) in pediatric patients.
Nine pediatric patients (5:4, girls:boys; 14.6 ± 2.0 years) with an SDHx-related mutation (SDHB:SDHA:SDHD, n = 7:1:1) were included in this retrospective study. At the time of initial diagnosis, 7/9 patients had metastatic disease. They underwent CT/MR imaging along with PET/CT using 68Ga-DOTATATE (n = 9), 18F–FDG (n = 8), and positron emission tomography-magnetic resonance imaging (PET/MR) using 18F–FDG (n = 1). In this manuscript, 18F–FDG PET/CT refers to both 18F–FDG PET/CT and 18F–FDG PET/MR. The per-lesion, per-region, and per-patient detection rates were compared and calculated for each of the imaging modalities. A composite of all functional and anatomic imaging studies served as the imaging comparator.
Eight out of nine patients were positive for PPGLs on the imaging studies that demonstrated 107 lesions in 22 anatomic regions on the imaging comparator. The per-lesion detection rates for 68Ga-DOTATATE PET/CT, 18F–FDG PET/CT, and CT/MR imaging were 93.5% (95%CI, 87.0% to 97.3%); 79.4% (95%CI, 70.5% to 86.6%); and 73.8% (95%CI, 64.5% to 81.9%), respectively. The per-lesion detection rate for 68Ga-DOTATATE PET/CT was significantly higher than that of 18F–FDG PET/CT (p = 0.001) or CT/MR imaging (p < 0.001). In all of the anatomic regions except abdomen, the per-lesion detection rates for 68Ga-DOTATATE PET/CT was found to be equal or superior to 18F–FDG PET/CT, and CT/MR imaging. The per-region detection rate was 100% (95%CI, 84.6% to 100%) for 68Ga-DOTATATE PET/CT and 90.9% (95%CI, 70.8% to 98.9%) for both 18F–FDG PET/CT and CT/MR imaging. The per-patient detection rates for 68Ga-DOTATATE PET/CT, 18FDG PET/CT, and CT/MR imaging were all 100% (95%CI, 63.1% to 100%).
Our preliminary study demonstrates the superiority of 68Ga-DOTATATE PET/CT in localization of SDHx-related PPGLs in pediatric population compared to 18F–FDG PET/CT and CT/MR imaging with the exception of abdominal (excluding adrenal and liver) lesions, and suggests that it might be considered as a first-line imaging modality in pediatric patients with SDHx-related PPGLs.
Keywords68Ga-DOTATATE FDG PET/CT Pediatric Pheochromocytoma Paraganglioma
We would like to thank Dr. Paul Wakim for the assistance in statistical analyses. We would also like to thank the patients and their families, for participating in the study, and all of the people who participated in this project, especially the technologists in the NIH Clinical Center PET Department.
This work was supported, in part, by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development and was supported, in part, by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute.
Compliance with ethical standards
This study was funded by National Institutes of Health (grant number: Z1AHD008735).
Conflict of interest
Author Abhishek Jha declares no conflict of interest. Author Alexander Ling declares no conflict of interest. Author Corina Millo declares no conflict of interest. Author Garima Gupta declares no conflict of interest. Author Bruna Viana declares no conflict of interest. Author Frank I. Lin declares no conflict of interest. Author Peter Herscovitch declares no conflict of interest. Author Karen T. Adams declares no conflict of interest. Author David Taïeb declares no conflict of interest. Author Adam R. Metwalli declares no conflict of interest. Author W. Marston Linehan declares no conflict of interest. Author Alessandra Brofferio declares no conflict of interest. Author Constantine A. Stratakis declares no conflict of interest. Author Electron Kebebew declares no conflict of interest. Author Maya Lodish declares no conflict of interest. Author Ali Cahid Civelek declares no conflict of interest. Author Karel Pacak declares no conflict of interest. Informed consent was obtained from all individual participants included in the study.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed assent from the patients and signed permission from one or both parents were obtained for all the individual participants included in the study.
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