Abstract
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Background: Pheochromocytoma (PHEO) is a rare neuroendocrine tumor arising from chromaffin cells of the adrenal gland which, undiagnosed, may potentially cause life-threatening complications due to overproduction of catecholamines, if remain undiagnosed. Around 5-10% of solitary PHEO are hereditary and are associated with mutations in about 22 susceptibility genes. Recently, 68Ga-DOTA(0)-Tyr(3)-octreotate (68Ga-DOTATATE) has shown excellent results in the localization of PHEO and paraganglioma (PGL). However, per EANM/SNMMI 2019 guidelines for radionuclide imaging of PHEO/PGL, 18F-L-dihydroxyphenylalanine (18F-FDOPA) is recommended as a positron emission tomography (PET) radiotracer of choice followed by 68Ga-DOTATATE and 18F-fluoro-2-deoxy-D-glucose (18F-FDG), respectively in the detection of sporadic PHEO. Thus far, no study has compared the diagnostic performance of these radiotracers in patients with apparently sporadic primary PHEO. The purpose of this prospective study was to evaluate and compare the diagnostic performances of 68Ga-DOTATATE, 18F-FDG, 18F-FDOPA, and 18F-fluorodopamine (18F-FDA) positron emission tomography-computed tomography (PET/CT), and computed tomography and/or magnetic resonance imaging (CT/MRI) in the detection of apparently sporadic primary PHEO.
Methods: Between October 2014 and October 2017, 68Ga-DOTATATE PET/CT was prospectively performed in 11 consecutive patients (females: males, 7:4; 51.9±16.8 years; age range, 20-74 years) with PHEO who subsequently tested negative for 22 susceptibility genes. All patients also underwent 18F-FDG PET/CT and CT/MRI. Additionally, 18F-FDOPA PET/CT was performed in 8/11 patients and 18F-FDA PET/CT in 6/11 patients. The mean duration between 68Ga-DOTATATE and 18F-FDG was 11±17 days, 2±1 days between 68Ga-DOTATATE and 18F-FDOPA, 14±19 days between 68Ga-DOTATATE and 18F-FDA, and, 12±17 days between 68Ga-DOTATATE and CT/MRI. The maximum standardized uptake value (SUVmax) of each PHEO in various PET/CT modalities were determined (Table 1). PHEO detection rates were also compared for all of the imaging modalities. All patients had surgical resection of PHEOs and histopathologic confirmation of PHEOs, thus serving as the reference standard for calculation of detection rates. For statistical analysis, the Mc Nemar test was used to compare the detection rates between 68Ga-DOTATATE PET/CT and other imaging modalities. Two-sided p values <0.05 were considered significant.
Results: Physiologic activity in normal adrenal was easily differentiated from PHEOs on 68Ga-DOTATATE PET/CT. The mean size of PHEO was found to be 4.3±2.7 and ranged from 2.0 to 9.5 cm. 68Ga-DOTATATE PET/CT demonstrated a PHEO detection rate of 11/11 [100%, 95% confidence interval (CI): 71.5-100%] (Table 1). 18F-FDG PET/CT, 18F-FDOPA PET/CT, 18F-FDA PET/CT, and CT/MRI showed PHEO detection rates of 9/11 (81.8%, 95% CI: 48.2-97.7%), 8/8 (100%, 95% CI: 63.1-100%), 6/6(100%, 95% CI: 54.1-100%), and 10/11 (90.9%, 95% CI: 58.7-99.7%), respectively (Table 1). A statistical significance (p<0.05) could not be achieved for the difference in detection rates between any of the imaging modalities. A representative figure demonstrates radiotracer uptake and detection of right PHEO on axial fused PET/CT images of 68Ga-DOTATATE (A), 18F-FDOPA (B), and 18F-FDA (C) whereas, there was no uptake on 18F-FDG (D).
Conclusions: In this small cohort of patients, the detection rates by 68Ga-DOTATATE PET/CT and 18F-FDA were found to be equal to 18F-FDOPA PET/CT in the diagnosis of apparently sporadic PHEO and hence can also be considered as the first choice of radionuclide imaging depending upon their availability. Table 1. Detection rate (%) for PET/CT utilizing 68Ga-DOTATATE, 18F-FDG, 18F-FDOPA, and 18F-FDA, and CT/MR imaging in apparently sporadic pheochromocytoma. $$table_{7B753A06-0C15-433E-A8E7-CD56524241AD} $$
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