Janssen Ingo, Chen Clara C, Zhuang Zhenping, Millo Corina M, Wolf Katherine I, Ling Alexander, Lin Frank I, Adams Karen T, Herscovitch Peter, Feelders Richard A, Fojo Antonio T, Taieb David, Kebebew Electron, Pacak Karel
Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Department of Radiology and Nuclear Medicine, Section of Nuclear Medicine, University Hospital Schleswig Holstein, Lübeck, Germany.
J Nucl Med. 2017 Aug;58(8):1236-1242. doi: 10.2967/jnumed.116.187690. Epub 2017 Mar 23.
Pheochromocytoma/paraganglioma (PPGL) syndromes associated with polycythemia have previously been described in association with mutations in the von Hippel-Lindau gene. Recently, mutations in the prolyl hydroxylase gene () 1 and 2 and in the hypoxia-inducible factor 2 α () were also found to be associated with multiple and recurrent PPGL. Such patients also presented with PPGL and polycythemia, and later on, some presented with duodenal somatostatinoma. In additional patients presenting with PPGL and polycythemia, no further mutations have been discovered. Because the functional imaging signature of patients with PPGL-polycythemia syndromes is still unknown, and because these tumors (in most patients) are multiple, recurrent, and metastatic, the goal of our study was to assess the optimal imaging approach using 4 different PET radiopharmaceuticals and CT/MRI in these patients. Fourteen patients (10 women, 4 men) with confirmed PPGL and polycythemia prospectively underwent Ga-DOTATATE (13 patients), F-FDG (13 patients), F-fluorodihydroxyphenylalanine (F-FDOPA) (14 patients), F-fluorodopamine (F-FDA) (11 patients), and CT/MRI (14 patients). Detection rates of PPGL lesions were compared between all imaging studies and stratified between the underlying mutations. F-FDOPA and F-FDA PET/CT showed similar combined lesion-based detection rates of 98.7% (95% confidence interval [CI], 92.7%-99.8%) and 98.3% (95% CI, 90.9%-99.7%), respectively. The detection rates for Ga-DOTATATE (35.3%; 95% CI, 25.0%-47.2%), F-FDG (42.3; 95% CI, 29.9%-55.8%), and CT/MRI (60.3%; 95% CI, 48.8%-70.7%) were significantly lower ( < 0.01), irrespective of the mutation status. F-FDOPA and F-FDA are superior to F-FDG, Ga-DOTATATE, and CT/MRI and should be the radiopharmaceuticals of choice in this rare group of patients.
此前已报道与红细胞增多症相关的嗜铬细胞瘤/副神经节瘤（PPGL）综合征与冯·希佩尔-林道基因的突变有关。最近，还发现脯氨酰羟化酶基因1和2以及缺氧诱导因子2α的突变与多发性和复发性PPGL相关。这类患者也表现为PPGL和红细胞增多症，后来，一些患者还出现十二指肠生长抑素瘤。在其他表现为PPGL和红细胞增多症的患者中，未发现进一步的突变。由于PPGL-红细胞增多症综合征患者的功能成像特征仍不清楚，并且由于这些肿瘤（在大多数患者中）是多发性、复发性和转移性的，我们研究的目的是评估在这些患者中使用4种不同的PET放射性药物和CT/MRI的最佳成像方法。14例确诊为PPGL和红细胞增多症的患者（10名女性，4名男性）前瞻性地接受了镓-多柔比星（13例患者）、氟代脱氧葡萄糖（13例患者）、氟代二羟基苯丙氨酸（F-FDOPA）（14例患者）、氟代多巴胺（F-FDA）（11例患者）以及CT/MRI（14例患者）检查。比较了所有成像研究中PPGL病变的检出率，并根据潜在突变进行分层。F-FDOPA和F-FDA PET/CT显示基于病变的联合检出率相似，分别为98.7%（95%置信区间[CI]，92.7%-99.8%）和98.3%（95%CI，90.9%-99.7%）。无论突变状态如何，镓-多柔比星（35.3%；95%CI，25.0%-47.2%）、氟代脱氧葡萄糖（42.3%；95%CI，29.9%-55.8%）和CT/MRI（60.3%；95%CI，48.8%-70.7%）的检出率显著较低（P<0.01）。F-FDOPA和F-FDA优于氟代脱氧葡萄糖、镓-多柔比星和CT/MRI，应该是这类罕见患者的首选放射性药物。
