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J Nucl Med. 2015 Jun;56(6):839-46. doi: 10.2967/jnumed.115.154815. Epub 2015 Apr 16.

Semiquantitative 123I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters.

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  • 1Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
  • 2Division of Vascular Medicine, Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
  • 3Institute of Pathology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • 4Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands Department of Pathology, Maastricht University Medical Centre, Maastricht, The Netherlands.
  • 5Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands; and.
  • 6Department of Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
  • 7Division of Endocrinology, Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands


(123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy plays an important role in the diagnostic evaluation of patients with pheochromocytoma and paraganglioma (PPGL). (123)I-MIBG targets cell membrane and vesicular catecholamine transporters of chromaffin cells and facilitates localization of the primary tumor and metastatic lesions. Its specificity for the diagnosis of adrenomedullary chromaffin cell tumors can be jeopardized by physiologic uptake by the normal adrenal medulla. The aim of this study was to distinguish between PPGLs and normal adrenal glands by evaluating semiquantitative (123)I-MIBG uptake and to examine genotype-specific differences in correlation with expression of catecholamine transporter systems.


Sixty-two PPGLs collected from 57 patients with hereditary mutations in SDHA (n = 1), SDHB (n = 2), and SDHD (n = 4) (SDH is succinate dehydrogenase); von Hippel-Lindau (VHL; n = 2); RET (n = 12); neurofibromin 1 (NF1; n = 2); and MYC-associated factor X (MAX; n = 1), and with sporadic PPGLs (n = 33) were investigated. Preoperative planar and SPECT images were semiquantitatively analyzed using uptake measurements. Tumor-to-liver and normal adrenal-to-liver ratios were calculated and correlated with clinical characteristics including genotype, tumor size, and plasma metanephrines concentrations. The expression of norepinephrine transporter (NET) and vesicular monoamine transporter (VMAT-1) was evaluated immunohistochemically in paraffin-embedded tumor tissues.


Mean tumor-to-liver ratios of PPGL lesions were significantly higher than normal adrenal-to-liver ratios (P < 0.001). Cutoff values to distinguish between physiologic and pathologic adrenal uptake were established at 0.7 (100% sensitivity, 10.3% specificity) and 4.3 (100% specificity, 66.1% sensitivity). No statistically significant differences in (123)I-MIBG uptake were found across PPGLs of different genotypes. Mean NET expression in hereditary cluster 2 (RET, NF1, MAX) and apparently sporadic tumors was significantly higher than for hereditary cluster 1 (SDHx, VHL) PPGLs (P = 0.011 and 0.006, respectively). Mean VMAT-1 expression in hereditary cluster 1 PPGLs was significantly higher than for cluster 2 tumors (P = 0.010). (123)I-MIBG uptake significantly correlated with maximum tumor diameter (P = 0.002). (123)I-MIBG uptake, however, did not correlate with either NET or VMAT-1 expression.


Liver-normalized semiquantitative (123)I-MIBG uptake may be helpful to distinguish between pheochromocytoma and physiologic adrenal uptake. Genotype-specific differences in the expression of NET and VMAT-1 do not translate into differences in (123)I-MIBG uptake.


123I-metaiodobenzylguanidine; norepinephrine transporter; paraganglioma; pheochromocytoma; scintigraphy; vesicular monoamine transporter 1

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