Diagnosis of pheochromocytoma and paraganglioma: Functional characterization of genotypic and phenotypic variants

嗜铬细胞瘤和副神经节瘤的诊断：基因型和表型变异的功能特征

• 批准号: 252408643
• 负责人: Dr. Roland Wolfgang Därr
• 金额: --
• 依托单位: National Institute of Child Health and Human Development
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/252408643?language=en
• 关键词: Diagnosis; pheochromocytoma; paraganglioma; Functional; characterization

Pheochromocytomas/paragangliomas (P/PGLs) are rare catecholamine-producing chromaffin cell tumors that typically arise from the adrenal gland but also from sympathetic extra-adrenal paraganglia and constitute a surgically correctable cause of chronic hypertension. The clinical features, and at times, life-threatening consequences of these tumours are highly dependent on the type and quantity of synthesized catecholamines, which may be released continuously in the blood circulation but also in sudden bouts either spontaneously or as a result of stimuli that normally would not pose a hazard, such as strenuous exercise, surgery, general anesthesia, and childbirth. The diagnosis of P/PGLs relies primarily on measurements of catecholamines and their metabolites in plasma and urine, standard dynamic testing such as the clonidine suppression test and the glucagon stimulation test, various nuclear imaging procedures, as well as computed tomographic (CT) and magnetic resonance (MR) imaging. However, despite of these well established procedures, the diagnosis and localization of P/PGLs can be challenging. This holds especially true for intra-abdominally located -biochemically silent- or poorly differentiated malignant P/PGLs where measurements of catecholamines and their metabolites and radio-iodinated metaiodobenzylguanidine (MIBG) scintigraphy can yield false-negative results in patients harbouring the tumour. Also, the informational value of dynamic testing is largely determined by the type of synthesized catecholamines. Finally, CT and MR imaging lack sufficient specificity. The present proposal focuses on the comparison of the diagnostic performance of positron emission tomography (PET)/CT and/or PET/MR scanning using the novel radiotracers [18F]-6F-dopamine ([18F]-6F-DA), [18F]-L-3,4-dihydroxyphenylalanine ([18F]-DOPA) und [68Ga]-DOTA-[Tyr3]-octreotate ([68Ga]-DOTATATE) for the diagnosis and localization of P/PGLs in patients with defined clinical and biochemical phenotypes, tumour-associated germline mutations, and pathohistological features. Furthermore, the benefits of romidepsin pre-treatment for uptake enhancement of [123I]-MIBG will be evaluated in selected cases. The results of these investigations should allow for the development of rational algorithms for the diagnosis or exclusion of P/PGLs and will possibly translate into novel treatment options in patients with malignant P/PGLs.

嗜铬细胞瘤/副神经节瘤（P/PGLs）是一种罕见的产生儿茶酚胺的嗜铬细胞瘤，通常起源于肾上腺，但也起源于肾上腺外交感副神经节，是一种可通过手术纠正的慢性高血压病因。这些肿瘤的临床特征和有时危及生命的后果高度依赖于合成儿茶酚胺的类型和数量，儿茶酚胺可能会在血液循环中持续释放，但也会突然发作，要么是自发的，要么是由于剧烈运动、手术、全身麻醉和分娩等通常不会造成危害的刺激。P/ pgl的诊断主要依赖于血浆和尿液中儿茶酚胺及其代谢物的测量，标准的动态测试，如可乐定抑制试验和胰高血糖素刺激试验，各种核成像程序，以及计算机断层扫描（CT）和磁共振（MR）成像。然而，尽管有这些完善的程序，但P/ pgl的诊断和定位可能具有挑战性。这尤其适用于腹腔内定位-生化沉默-或低分化的恶性P/ pgl，其中儿茶酚胺及其代谢物和放射性碘化间氧苄基胍（MIBG）闪烁成像可在肿瘤患者中产生假阴性结果。此外，动态检测的信息价值在很大程度上取决于合成儿茶酚胺的类型。最后，CT和MR成像缺乏足够的特异性。本研究的重点是比较正电子发射断层扫描(PET)/CT和/或PET/MR扫描使用新型放射性示踪剂[18F]- 6f -多巴胺（[18F]- 6f - da）、[18F]- l -3,4-二羟基苯丙氨酸（[18F]- dopa）和[68Ga]- dota -[Tyr3]-octreotate （[68Ga]- dotatate）对具有明确临床和生化表型、肿瘤相关种系突变和病理组织学特征的患者的P/PGLs诊断和定位的诊断性能。此外，将在选定的病例中评估罗咪地辛预处理对[123I]-MIBG摄取增强的益处。这些研究的结果应该允许开发合理的算法来诊断或排除P/ pgl，并可能转化为恶性P/ pgl患者的新治疗方案。

项目成果

Phase II clinical trial of axitinib in metastatic pheochromocytomas and paraganlgiomas (P/PG): Preliminary results.

阿西替尼治疗转移性嗜铬细胞瘤和副神经节瘤（P/PG）的II期临床试验：初步结果

• DOI: 10.1200/jco.2015.33.7_suppl.457
• 发表时间: 2015
• 期刊: Journal of Clinical Oncology
• 影响因子: 45.3
• 作者: Burotto-Pichun ME;Edgerly M;Velarde M;Bates SE;Därr R;Adams KT;Pacak K;Fojo T
• 通讯作者: Fojo T