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

Abstract

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. Methods: Sixty-two PPGLs collected from 57 patients with hereditary mutations in SDHA (n 5 1), SDHB (n 5 2), and SDHD (n 5 4) (SDH is succinate dehydrogenase); von Hippel-Lindau (VHL; n 5 2); RET (n 5 12); neurofibromin 1 (NF1; n 5 2); and MYC-associated factor X (MAX; n 5 1), and with sporadic PPGLs (n 5 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 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 5 0.011 and 0.006, respectively). Mean VMAT-1 expression in hereditary cluster 1 PPGLs was significantly higher than for cluster 2 tumors (P 5 0.010). 123 I-MIBG uptake significantly correlated with maximum tumor diameter (P 5 0.002). 123 I-MIBG uptake, however, did not correlate with either NET or VMAT-1 expression. Conclusion: 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.

Clinical Usefulness of 99mTc-HYNIC-TOC and 131I-MIBG Scintigraphy in the Evaluation of Adrenal Tumors

“…MIBG imaging has been well established as a localizing tool and a functional marker of catecholamine secreting tissue, with a high sensitivity range (83%-100%) and a high specificity (95-100%) (24,25,30). MIBG demonstrated a high diagnostic accuracy in four patients, who had pheochromocytomas confirmed by histopathology and were positive on the MIBG scan.…”

“…Conversely, due to its high sensitivity 99m Tc-HYNIC-TOC scintigraphy can be considered as the first choice scintigraphic imaging technique in paragangliomas. (24,25,30,31,39).…”

“…Although 131Iand 123 I-metaiodobenzylguanidine (MIBG), a norepinephrine analogue whose uptake is proportional to the number of neurosecretory granules within the tumour, is the most common functional imaging technique used in the assessment of pheochromocytomas (21,22,24,25), the scintigraphic evaluation of patients with adrenocortical tumours is currently limited (13,19,20,23).…”

Functional Imaging of Paragangliomas with an Emphasis on Von Hippel–Lindau-Associated Disease: A Mini Review

“…However, subjects with VHL have lower VMATs expression in chromaffin tissue, possibly hampering the use of MIBG as an effective functional imaging agent ( 29 , 30 ). Additionally, 123 I-MIBG uptake was not correlated with either hNET or VMAT (VMAT-1 in particular) expression in a series of 62 patients with PHEOs/PGLs, including two patients with VHL ( 31 ). In a comparison between VHL patients and SHDB patients, a study found that MIBG was overall positive in 11/12 VHL patients but was falsely negative in 3/5 VHL patients with synchronous bilateral adrenal PHEOs ( 32 ).…”

Opening the door to noninvasive assessment of cardiac transplant rejection: It’s all in the preparation

“…9 The role of heparin lies in its ability to activate lipoprotein lipase which leads to an increase in the supply of fatty acids. 10 18 FDG PET images are subsequently interpreted using a variety of methods, including visual review of the 18 FDG images, a semiquantitative scale and standardized uptake values (SUVs).…”