Purpose Patients with succinate dehydrogenase subunit B (SDHB) mutation-related pheochromocytoma/paraganglioma (PHEO/PGL) are at a higher risk for metastatic disease than other hereditary PHEOs/PGLs. Current therapeutic approaches are limited but the best outcomes are based on the early and proper detection of as many lesions as possible. Because PHEOs/PGLs overexpress somatostatin receptor 2 (SSTR2), the goal of our study was to assess the clinical utility of [68Ga]-DOTA(0)-Tyr(3)-octreotate ([68Ga]-DOTATATE) positron emission tomography/computed tomography (PET/CT) and to evaluate its diagnostic utility in comparison to the currently recommended functional imaging modalities [18F]-fluorodopamine ([18F]-FDA), [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA), [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) PET/CT as well as CT/magnetic resonance imaging (MRI). Experimental Design [68Ga]-DOTATATE PET/CT was prospectively performed in 17 patients with SDHB-related metastatic PHEOs/PGLs. All patients also underwent [18F]-FDG PET/CT and CT/MRI with 16 of the 17 patients also receiving [18F]-FDOPA and [18F]-FDA PET/CT scans. Detection rates of metastatic lesions were compared between all these functional imaging studies. A composite synthesis of all used functional and anatomical imaging studies served as the imaging comparator. Results [68Ga]-DOTATATE PET/CT demonstrated a lesion-based detection rate of 98.6% (95% confidence interval (CI) 96.5% to 99.5%), [18F]-FDG, [18F]-FDOPA, [18F]-FDA PET/CT, and CT/MRI showed detection rates of 85.8% (CI 81.3% to 89.4%) (p<0.01), 61.4% (CI 55.6% to 66.9%) (p<0.01), 51.9% (CI 46.1% to 57.7%) (p<0.01), and 84.8% (CI 80.0% to 88.5%) (p<0.01), respectively. Conclusions [68Ga]-DOTATATE PET/CT showed a significantly superior detection rate compared to all other functional and anatomical imaging modalities and may represent the preferred future imaging modality in the evaluation of SDHB-related metastatic PHEO/PGL.

Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors (SSTRs) and recent studies have already shown excellent results in the localization of sympathetic succinate dehydrogenase complex, subunit B (SDHB) mutation-related metastatic PHEOs/PGLs using [(68Ga)-DOTA0,Tyr3]Octreotate ([68Ga]-DOTATATE) positron emission tomography/computed tomography (PET/CT). Therefore, the goal of our study was to assess the clinical utility of this functional imaging modality in parasympathetic head and neck paragangliomas (HNPGLs) compared to anatomical imaging with CT/MRI and other functional imaging modalities, including [18F]-fluorohydroyphenylalanine ([18F]-FDOPA) PET/CT, currently the gold standard in the functional imaging of HNPGLs. Methods [68Ga]-DOTATATE PET/CT was prospectively performed in 20 patients with HNPGLs. All patients also underwent [18F]-FDOPA PET/CT, [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) PET/CT, and CT/MRI, with 18 patients also receiving [18F]-fluorodopamine ([18F]-FDA) PET/CT. [18F]-FDOPA PET/CT and CT/MRI served as the imaging comparators. Results Thirty-eight lesions in 20 patients were detected, with [18F]-FDOPA PET/CT identifying 37 of 38 (37/38) and CT/MRI identifying 22 of 38 lesions (22/38, p<0.01). All 38 and additional 7 lesions (p=0.016) were detected on [68Ga]-DOTATATE PET/CT. Significantly fewer lesions were identified by [18F]-FDG PET/CT (24/38, p<0.01) and [18F]-FDA PET/CT (10/34, p<0.01). Conclusion [68Ga]-DOTATATE PET/CT identified more lesions than the other imaging modalities. Due to the results of the present study, including the increasing availability and use of DOTA-analogs in the therapy of neuroendocrine tumors, we expect that [68Ga]-DOTATATE PET/CT will become the preferred functional imaging modality for HNPGLs in the near future.

The syndrome of paraganglioma (PGL), somatostatinoma (SOM), and early childhood polycythemia in patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A) gene is described in only a few patients worldwide. The present study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings these experiences into perspective with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11–46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with secondary polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8–38) and SOMs at 29 years (range 22–38). PGLs were multiple, recurrent, and metastatic in 100%, 100%, and 29% of all cases, and SOMs in 40%, 40%, and 60%, respectively. All PGLs were primarily norepinephrine producing. All patients had abnormal ophthalmologic findings and those with SOMs had gallbladder disease. Computed tomography (CT) and magnetic resonance imaging revealed cystic lesions at multiple sites and hemangiomas in 4 patients (57%), previously thought to be pathognomonic for von Hippel-Lindau disease. The most accurate radiopharmaceutical to detect PGL appeared to be [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA). Therefore, [18F]-FDOPA PET/CT, not [68Ga]-(DOTA)-[Tyr3]-octreotate ([68Ga]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The long-term prognosis of the syndrome is unknown. However, to date no deaths occurred after 6 years follow-up. Physicians should be aware of this unique syndrome and its diagnostic and therapeutic challenges.

The results of this study demonstrate the superiority of (68)Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality.