Ingo Janssen

68Ga-DOTATATE PET/CT in the Localization of Head and Neck Paragangliomas Compared with Other Functional Imaging Modalities and CT/MRI

Pheochromocytomas/paragangliomas overexpress somatostatin receptors, and recent studies have already shown excellent results in the localization of sympathetic succinate dehydrogenase complex, subunit B, mutation-related metastatic pheochromocytomas/paragangliomas using 68Ga-DOTATATE 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 with anatomic 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-FDG PET/CT, and CT/MRI, with 18 patients also undergoing 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 and CT/MRI identifying 23 of 38 lesions (P < 0.01). All 38 and an 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 other imaging modalities. With the results of the present study, and 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.

Novel insights into the polycythemia-paraganglioma-somatostatinoma syndrome

Worldwide, the syndromes of paraganglioma (PGL), somatostatinoma (SOM) and early childhood polycythemia are described in only a few patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A). This study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings into perspective these experiences 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 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.

Functional imaging signature of patients presenting with polycythemia/paraganglioma syndromes

Pheochromocytoma/paraganglioma (PPGL) syndromes associated with polycythemia have previously been described in association with mutations in the von Hippel–Lindau gene. Recently, mutations in the prolyl hydroxylase gene (PHD) 1 and 2 and in the hypoxia-inducible factor 2 α (HIF2A) were also found to be associated with multiple and recurrent PPGL. Such patients also presented with PPGL and polycythemia, and later on, some presented with duodenal somatostatinoma. In additional patients presenting with PPGL and polycythemia, no further mutations have been discovered. Because the functional imaging signature of patients with PPGL–polycythemia syndromes is still unknown, and because these tumors (in most patients) are multiple, recurrent, and metastatic, the goal of our study was to assess the optimal imaging approach using 4 different PET radiopharmaceuticals and CT/MRI in these patients. Methods: Fourteen patients (10 women, 4 men) with confirmed PPGL and polycythemia prospectively underwent 68Ga-DOTATATE (13 patients), 18F-FDG (13 patients), 18F-fluorodihydroxyphenylalanine (18F-FDOPA) (14 patients), 18F-fluorodopamine (18F-FDA) (11 patients), and CT/MRI (14 patients). Detection rates of PPGL lesions were compared between all imaging studies and stratified between the underlying mutations. Results: 18F-FDOPA and 18F-FDA PET/CT showed similar combined lesion-based detection rates of 98.7% (95% confidence interval [CI], 92.7%–99.8%) and 98.3% (95% CI, 90.9%–99.7%), respectively. The detection rates for 68Ga-DOTATATE (35.3%; 95% CI, 25.0%–47.2%), 18F-FDG (42.3; 95% CI, 29.9%–55.8%), and CT/MRI (60.3%; 95% CI, 48.8%–70.7%) were significantly lower (P < 0.01), irrespective of the mutation status. Conclusion: 18F-FDOPA and 18F-FDA are superior to 18F-FDG, 68Ga-DOTATATE, and CT/MRI and should be the radiopharmaceuticals of choice in this rare group of patients.

Functional Imaging Experience in a Germline Fumarate Hydratase Mutation–Positive Patient With Pheochromocytoma and Paraganglioma

ABSTRACT Objective: To report the functional imaging experience with a 29-year-old woman carrying a mutation in the fumarate hydratase (FH)-encoding gene and a history of a pheochromocytoma (PHEO) and retroperitoneal paraganglioma (PGL). Methods: The patient was found to have a splice-site mutation in the FH gene at intron 2, c.268-2A>G. To confirm this, immunohistochemical staining was performed on tumor tissue slides from the patients previous surgeries. The patient underwent biochemical testing for PHEO/PGL, which included chromogranin A and plasma methoxytyramine. The patients tumors were also imaged using several imaging modalities, including computed tomography (CT), magnetic resonance imaging, ultrasound, and positron emission tomography (PET)/CT studies using [18F]-fluorodeoxyglucose ([18F]-FDG), [18F]-fluorodopamine ([18F]-FDA), [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA), and [68Ga]-tetraazacyclododecanetetraacetic acid–[Tyr3]-octreotate ([68Ga]-DOTATATE) as tracers. Results: The patient ...

Imaging Modalities for Pheochromocytoma and Paraganglioma

Pheochromocytomas and extra-adrenal paragangliomas, associated with the sympathetic nervous system, are rare neuroendocrine tumors of neural crest origin. These tumors behave differently from those associated with the parasympathetic system (i.e., head and neck paragangliomas). This chapter will particularly emphasize current and emerging knowledge of imaging options in these tumors.

Radionuclide Imaging of Head and Neck Paragangliomas

Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors belonging to the family of pheochromocytoma/paraganglioma neoplasms. These tumors are specifically associated with the parasympathetic nervous system and therefore behave differently from those associated with the sympathetic nervous system (i.e., chromaffin tumors). This chapter will particularly emphasize current and emerging knowledge of imaging options on these tumors.

Relevant Discordance Between 68Ga-DOTATATE and 68Ga-DOTANOC in SDHB-Related Metastatic Paraganglioma: Is Affinity to Somatostatin Receptor 2 the Key?

Pheochromocytomas/paragangliomas are somatostatin receptor 2-overexpressing tumors. Ga-DOTA-peptide imaging has recently shown excellent results in the detection of metastatic lesions in these tumors. However, currently used Ga-DOTA peptides show different somatostatin receptor affinities. Here, we report the remarkable differences in a patient who was imaged with Ga-DOTANOC and Ga-DOTATATE PET/CT within a 7-month period. The patient presented with a nearly negative Ga-DOTANOC PET/CT scan, whereas on Ga-DOTATATE PET/CT, multiple highly positive lesions were identified.

Rapidly Growing Chest Wall Mass in a Case of Sporadic Metastatic Paraganglioma: Imaging With 4 Different PET Radiopharmaceuticals.

Pheochromocytomas/paragangliomas (PGLs) are rare tumors and mostly benign. We report on a 32-year-old woman with metastatic PGL who was first diagnosed with an abdominal PGL at the age of 12 years. She soon developed metastatic disease and received several treatments including external beam radiation and chemotherapy. When she was referred to our institution in 2014, her major complaint was a rapidly growing chest wall mass on the left side. The patient was imaged at our institution with 4 different PET radiopharmaceuticals.