Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma
Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma
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DOI：
10.1161/hypertensionaha.117.09975
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发表时间：
2018-02-01
期刊：
影响因子：
8.3
通讯作者：
Hahner, Stefanie
中科院分区：
文献类型：
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作者：
Heinze, Britta;Fuss, Carmina T.;Hahner, Stefanie
原发性醛固酮增多症是继发性高血压最常见的原因，与高血压对照组相比，它与发病率和死亡率增加有关。主要的诊断挑战是区分双侧和单侧疾病，这决定了治疗方案。目前推荐用于鉴别诊断的双侧肾上腺静脉采样是一种有创的方法，有几个缺点，因此开发新的非侵入性诊断工具是可取的。在用实时定量聚合酶链式反应和免疫组织化学方法研究趋化因子受体的表达模式时，我们观察到CXCR4(CXC趋化因子受体4型)在正常肾上腺组织、肾上腺皮质瘤旁的肾上腺皮质和醛固酮腺瘤(APA)中高表达，并与CYP11B2(醛固酮合成酶)的表达密切相关。相反，在大多数经常巧合发现的无功能腺瘤中没有检测到CXCR4。特异性CXCR4配体68Ga-pentixafor最近被确定为用于CXCR4表达的分子成像的放射性示踪剂，并在我们的研究中显示出与APA冰冻切片强烈而特异的结合。我们对9例APA所致的原发性醛固酮增多症患者进行了68Ga-Pentixafor正电子发射断层扫描。与其他原因的68Ga-Pentixafor正电子发射断层扫描相比，APAS患者肾上腺皮质醛固酮分泌增加一侧的示踪剂摄取量显著高于其他原因患者。因此，通过CXCR4特异性配体对产生醛固酮的组织进行分子成像，可能是一种非常有希望的非侵入性描述APAs患者的工具。
Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with increased morbidity and mortality compared with hypertensive controls. The central diagnostic challenge is the differentiation between bilateral and unilateral disease, which determines treatment options. Bilateral adrenal venous sampling, currently recommended for differential diagnosis, is an invasive procedure with several drawbacks, making it desirable to develop novel noninvasive diagnostic tools. When investigating the expression pattern of chemokine receptors by quantitative real-time polymerase chain reaction and immunohistochemistry, we observed high expression of CXCR4 (CXC chemokine receptor type 4) in aldosterone-producing tissue in normal adrenals, adjacent adrenal cortex from adrenocortical adenomas, and in aldosterone-producing adenomas (APA), correlating strongly with the expression of CYP11B2 (aldosterone synthase). In contrast, CXCR4 was not detected in the majority of nonfunctioning adenomas that are frequently found coincidently. The specific CXCR4 ligand 68Ga-pentixafor has recently been established as radiotracer for molecular imaging of CXCR4 expression and showed strong and specific binding to cryosections of APAs in our study. We further investigated 9 patients with primary aldosteronism because of APA by 68Ga-pentixafor-positron emission tomography. The tracer uptake was significantly higher on the side of increased adrenocortical aldosterone secretion in patients with APAs compared with patients investigated by 68Ga-pentixafor-positron emission tomography for other causes. Molecular imaging of aldosterone-producing tissue by a CXCR4-specific ligand may, therefore, be a highly promising tool for noninvasive characterization of patients with APAs.