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Tomá Zelinka^1,5, Henri J L M Timmers¹, Anna Kozupa¹, Clara C Chen², Jorge A Carrasquillo², James C Reynolds², Alexander Ling³, Graeme Eisenhofer⁴, Ivica Lazúrová⁶, Karen T Adams¹, Millie A Whatley², Jií Widimsk, Jr⁵ and Karel Pacak¹

¹ Reproductive Biology and Medicine Branch, National Institutes of Child Health and Human Development² Nuclear Medicine Department, ³ Department of Diagnostic Radiology and ⁴ Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA⁵ 3rd Department of Medicine, 1st Faculty of Medicine, General Faculty Hospital, U Nemocnice 1, Prague 2, 128 08, Czech Republic⁶ Department of Medicine, P. J. afaík University, SNP 1, Koice, 041 66, Slovak Republic

(Correspondence should be addressed to K Pacak who is now at Section on Medical Neuroendocrinology, Reproductive Biology and Medicine Branch, National Institutes of Child Health and Human Development, 10 Center Drive, Building 10, CRC, RM 1-E 3140, MSC 1109, Bethesda, Maryland 20892-1109, USA; Email: karel{at}mail.nih.gov)

We performed a retrospective analysis of 71 subjects with metastatic pheochromocytoma and paraganglioma (30 subjects with mutation of succinate dehydrogenase enzyme subunit B (SDHB) gene and 41 subjects without SDHB mutation). Sixty-nine percent presented with bone metastases (SDHB +/–: 77% vs 63%), 39% with liver metastases (SDHB +/–: 27% vs 47%), and 32% with lung metastases (SDHB +/–: 37% vs 29%). The most common sites of bone involvement were thoracic spine (80%; SDHB+/–: 83% vs 77%), lumbar spine (78%; SDHB +/–: 78% vs 75%), and pelvic and sacral bones (78%; SDHB +/–: 91% vs 65%, P=0.04). Subjects with SDHB mutation also showed significantly higher involvement of long bones (SDHB +/–: 78% vs 30%, P=0.007) than those without the mutation. The best overall sensitivity in detecting bone metastases demonstrated positron emission tomography (PET) with 6-[¹⁸F]-fluorodopamine ([¹⁸F]-FDA; 90%), followed by bone scintigraphy (82%), computed tomography or magnetic resonance imaging (CT/MRI; 78%), 2-[¹⁸F]-fluoro-2-deoxy-D-glucose ([¹⁸F]-FDG) PET (76%), and scintigraphy with [^123/131I]-metaiodobenzylguanidine (71%). In subjects with SDHB mutation, imaging modalities with best sensitivities for detecting bone metastases were CT/MRI (96%), bone scintigraphy (95%), and [¹⁸F]-FDG PET (92%). In subjects without SDHB mutations, the modality with the best sensitivity for bone metastases was [¹⁸F]-FDA PET (100%). In conclusion, bone scintigraphy should be used in the staging of patients with malignant pheochromocytoma and paraganglioma, particularly in patients with SDHB mutations. As for PET imaging, [¹⁸F]-FDG PET is highly recommended in SDHB mutation patients, whereas [¹⁸F]-FDA PET is recommended in patients without the mutation.