PuSH - Publication Server of Helmholtz Zentrum München: Semi-quantitative <sup>123</sup>I-metaiodobenzylguanidine scintigraphy to distinguish pheochromocytoma and paraganglioma from physiological adrenal uptake and its correlation with genotype-dependent expression of catecholamine transporters.

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van Berkel, A.* ; Upendrao, J.* ; Lenders, J.* ; Pellegata, N.S. ; Kusters, B.* ; Piscaer, I.* ; Hermus, A.R.* ; Plantinga, T.S.* ; Langenhuijsen, H.* ; Vriens, D.* ; Janssen, M.* ; Gotthardt, M.* ; Timmers, H.*

Semi-quantitative ¹²³I-metaiodobenzylguanidine scintigraphy to distinguish pheochromocytoma and paraganglioma from physiological adrenal uptake and its correlation with genotype-dependent expression of catecholamine transporters.

J. Nucl. Med. 56, 839-846 (2015)

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(123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy plays an important role in the diagnostic evaluation of patients with pheochromocytoma and paraganglioma (PPGL). 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 physiological uptake by the normal adrenal medulla. The aim of this study was to distinguish between PPGLs and normal adrenal glands by evaluating semi-quantitative (123)I-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), SDHD (n = 4), VHL (n = 2), RET (n = 12), NF1 (n = 2), MAX (n = 1) and with sporadic PPGLs (n = 33) were investigated. Pre-operative planar and single-photon emission computed tomographic (SPECT) images were semi-quantitatively analyzed using uptake measurements. Tumor-to-liver (T/L) and normal-adrenal-to-liver (NA/L) 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 T/L ratios of PPGL lesions were significantly higher than NA/L ratios (p<0.001). Cut-off values to distinguish between physiological and pathological 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 P = 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). MIBG uptake, however, did not correlate with either NET or VMAT-1 expression. CONCLUSION: Liver normalized semi-quantitative (123)I-MIBG uptake may be helpful to distinguish between pheochromocytoma and physiological adrenal uptake. Genotype-specific differences in expression of NET and VMAT-1 do not translate into differences in (123)I-MIBG uptake.

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PuSH - Publication Server of Helmholtz Zentrum München

Semi-quantitative 123I-metaiodobenzylguanidine scintigraphy to distinguish pheochromocytoma and paraganglioma from physiological adrenal uptake and its correlation with genotype-dependent expression of catecholamine transporters.

Semi-quantitative ¹²³I-metaiodobenzylguanidine scintigraphy to distinguish pheochromocytoma and paraganglioma from physiological adrenal uptake and its correlation with genotype-dependent expression of catecholamine transporters.