RT Journal Article SR Electronic T1 Semiquantitative 123I-Metaiodobenzylguanidine Scintigraphy to Distinguish Pheochromocytoma and Paraganglioma from Physiologic Adrenal Uptake and Its Correlation with Genotype-Dependent Expression of Catecholamine Transporters JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 839 OP 846 DO 10.2967/jnumed.115.154815 VO 56 IS 6 A1 Anouk van Berkel A1 Jyotsna U. Rao A1 Jacques W.M. Lenders A1 Natalia S. Pellegata A1 Benno Kusters A1 Ianthe Piscaer A1 Ad R.M.M. Hermus A1 Theo S. Plantinga A1 Johan F. Langenhuijsen A1 Dennis Vriens A1 Marcel J.R. Janssen A1 Martin Gotthardt A1 Henri J.L.M. Timmers YR 2015 UL http://jnm.snmjournals.org/content/56/6/839.abstract AB 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy plays an important role in the diagnostic evaluation of patients with pheochromocytoma and paraganglioma (PPGL). 123I-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 123I-MIBG uptake and to examine genotype-specific differences in correlation with expression of catecholamine transporter systems. Methods: 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. Results: 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 123I-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). 123I-MIBG uptake significantly correlated with maximum tumor diameter (P = 0.002). 123I-MIBG uptake, however, did not correlate with either NET or VMAT-1 expression. Conclusion: Liver-normalized semiquantitative 123I-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 123I-MIBG uptake.