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Superiority of Fluorodeoxyglucose Positron Emission Tomography to Other Functional Imaging Techniques in the Evaluation of Metastatic SDHB-Associated Pheochromocytoma and Paraganglioma

Henri J.L.M. Timmers, Anna Kozupa, Clara C. Chen, Jorge A. Carrasquillo, Alexander Ling, Graeme Eisenhofer, Karen T. Adams, Daniel Solis, Jacques W.M. Lenders, Karel Pacak

From the Reproductive Biology and Medicine Branch, National Institutes of Child Health and Human Development; Nuclear Medicine Department; Department of Diagnostic Radiology; Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Department of Internal Medicine, Division of General Internal Medicine; and the Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands

Address reprint requests to Henri J.L.M. Timmers, MD, PhD, Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, 10 Center Dr, Bldg 10, CRC, RM 1-E 3140, MSC 1109, Bethesda MD 20892-1109; e-mail: h.timmers{at}endo.umcn.nl

Purpose: Germline mutations of the gene encoding subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB) predispose to malignant paraganglioma (PGL). Timely and accurate localization of these aggressive tumors is critical for guiding optimal treatment. Our aim is to evaluate the performance of functional imaging modalities in the detection of metastatic lesions of SDHB-associated PGL.

Patients and Methods: Sensitivities for the detection of metastases were compared between [¹⁸F]fluorodopamine ([¹⁸F]FDA) and [¹⁸F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), iodine-123- (¹²³I) and iodine-131 (¹³¹I) -metaiodobenzylguanidine (MIBG), ¹¹¹In-pentetreotide, and Tc-99m-methylene diphosphonate bone scintigraphy in 30 patients with SDHB-associated PGL. Computed tomography (CT) and magnetic resonance imaging (MRI) served as standards of reference.

Results: Twenty-nine of 30 patients had metastatic lesions. In two patients, obvious metastatic lesions on functional imaging were missed by CT and MRI. Sensitivity according to patient/body region was 80%/65% for ¹²³I-MIBG and 88%/70% for [¹⁸F]FDA-PET. False-negative results on ¹²³I-MIBG scintigraphy and/or [¹⁸F]FDA-PET were not predicted by genotype or biochemical phenotype. [¹⁸F]FDG-PET yielded a by patient/by body region sensitivity of 100%/97%. At least 90% of regions that were false negative on ¹²³I-MIBG scintigraphy or [¹⁸F]FDA-PET were detected by [¹⁸F]FDG-PET. In two patients, ¹¹¹In-pentetreotide scintigraphy detected liver lesions that were negative on other functional imaging modalities. Sensitivities were similar before and after chemotherapy or ¹³¹I-MIBG treatment, except for a trend toward lower post- (60%/41%) versus pretreatment (80%/65%) sensitivity of ¹²³I-MIBG scintigraphy.

Conclusion: With a sensitivity approaching 100%, [¹⁸F]FDG-PET is the preferred functional imaging modality for staging and treatment monitoring of SDHB-related metastatic PGL.

Supported by the Intramural Research Program of the National Institute of Child Health and Human Development/National Institutes of Health.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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