Evaluation of the Sensitivity and Specificity of<sup>11</sup>C-Metomidate Positron Emission Tomography (PET)-CT for Lateralizing Aldosterone Secretion by Conn's Adenomas

Burton, Timothy J.; Mackenzie, Isla S.; Balan, Kottekkattu; Koo, Brendan; Bird, Nick; Soloviev, D.; Azizan, Elena; Aigbirhio, Franklin I.; Gurnell, Mark; Brown, Morris J.

doi:10.1210/jc.2011-1537

Cited by 179 publications

(185 citation statements)

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“…42 Our observation of expression of both CYP11B1 and CYP11B2 in most APAs matches with the observed high 11C-metomidate uptake in the aldosteroneproducing tissue. 43,44 However, 98% of the NFAs in our series also exhibited CYP11B1 staining, and both 11C-metomidate uptake and 123 I-iodometomidate uptake in NFA have been demonstrated in clinical studies. 45,46 CYP11B1 downregulation may be achieved in normal surrounding adrenocortical tissue by dexamethasone pretreatment.…”

Section: Discussionmentioning

confidence: 53%

“…However, it is unclear whether this also holds true for adrenocortical adenoma cells because ACTH (adrenocorticotropic hormone) receptor expression is low in NFAs. 47 Nevertheless, the data obtained by the 11C-metomidate studies represent an important proof of principle demonstrating that the PET imaging technique per se may be of value in PA. 44 Targeting CXCR4 in PA may be a promising alternative approach. This is highlighted by our 9 patients with APA who were investigated by 68Ga-pentixafor PET/CT.…”

Section: Discussionmentioning

confidence: 99%

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Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma

Heinze¹,

Fuß²,

Mulatero³

et al. 2018

Hypertension

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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.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma

Heinze¹,

Fuß²,

Mulatero³

et al. 2018

Hypertension

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“…Our Receiver Operator Characteristics curves analysis supports this hypothesis: the AT1AA titer provided an accurate identification of APA patients among the hypertensive patients, and also a distinction between APA and IHA patients referred to the 2 centers. The latter distinction normally requires adrenal vein sampling or PET-CT (positron emission tomographycomputed tomography) with metomidate, 40 both of which are expensive and not readily available. Therefore the diagnostic discrimination provided by the AT1AA assay could be important from the clinical standpoint in that it might allow selecting a cohort of PA patients to be submitted to either test, owing to a higher risk of carrying a unilateral surgically correctable cause of PA.…”

Section: Discussionmentioning

confidence: 99%

Elevation of Angiotensin-II Type-1-Receptor Autoantibodies Titer in Primary Aldosteronism as a Result of Aldosterone-Producing Adenoma

et al. 2013

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A large prospective study showed that primary aldosteronism (PA) is the most prevalent form of endocrine hypertension among hypertensive patients referred to specialized hypertension centers. 1 The discrimination between its main subtypesaldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH, also referred to as idiopathic hyperaldosteronism, IHA)-is crucial, as the former is surgically curable, whereas the latter requires lifelong medical treatment.2,3 This distinction is, however, challenging because of the biochemical and pathological overlapping of APA and BAH, and the lack of well-defined functional and morphological criteria. The tissue surrounding the APA often contains multiple nodules and shows paradoxical hyperplastic changes. Furthermore, cases of multinodular adrenal hyperplasia have been reported, 4 even though their distinctive criteria from APA remain vague.Thus, a pathological continuum between APA and BAH featuring a transition from hyperplasia to a nodular phase has been proposed, 5 which suggests that pathogenic mechanisms common to these conditions exist. However, the stimuli driving this transition eluded identification thus far notwithstanding a long quest. For example, even though angiotensin-II type-1 (AT1) receptors were detected in both the normal adrenocortical zona glomerulosa and in APA, 6-8 angiotensin-II (Ang-II), one of the known secretagogues of aldosterone, is barely detectable in PA patients.Of interest, circulating autoantibodies against a specific epitope of the AT1 receptor (AT1AA) with specific agonistic activity have been suggested to play a pathogenic role in diseases characterized by vascular and renal damage, such as preeclampsia and malignant hypertension. 9-16These agonistic autoantibodies against type-1 angiotensin-II receptor (AT1AA) could stimulate aldosterone secretion and trigger the development of hyperplastic changes in the zona glomerulosa in PA patients. We therefore sought for AT1AA in serum of patients with PA and investigated whether their titer was higher Abstract-The mechanisms of excess aldosterone secretion in primary aldosteronism (PA) remain poorly understood, although a role for circulating factors has been hypothesized for decades. Agonistic autoantibodies against type-1 angiotensin-II receptor (AT1AA) are detectable in malignant hypertension and preeclampsia and might play a role in PA. Moreover, if they were elevated in aldosterone-producing adenoma (APA) and not in idiopathic hyperaldosteronism (IHA), they might be useful for discriminating between these conditions. To test these hypotheses, we measured the titer of AT1AA in serum of 46 patients with PA (26 with APA, 20 with IHA), 62 with primary hypertension (PH), 13 preeclamptic women, and 45 healthy normotensive blood donors.We found that the AT1AA titer was higher (P<0.

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“…In addition, one center has used the 11 C-metomidate positron emission tomography-CT to confirm the validity of AVS performed on limited MR blockade. 31 Catheterization of the left adrenal vein is achieved in almost 100% of the cases if the catheter tip is positioned either at or distal to the orifice of the left inferior phrenic vein to avoid a major dilution effect; in contrast, that of the right adrenal vein is more difficult owing to its small size and its draining directly into the inferior vena cava (IVC) at various angles or directly into a small accessory hepatic vein. 10,11 Hence, prior knowledge of the right adrenal vein anatomy can facilitate catheterization in difficult cases.…”

Section: Preparation Of the Patient And Performance Of Avsmentioning

confidence: 99%

An Expert Consensus Statement on Use of Adrenal Vein Sampling for the Subtyping of Primary Aldosteronism

et al. 2014

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Abstract-Adrenal venous sampling is recommended by current guidelines to identify surgically curable causes of hyperaldosteronism but remains markedly underused. Key factors contributing to the poor use of adrenal venous sampling include the prevailing perceptions that it is a technically challenging procedure, difficult to interpret, and can be complicated by adrenal vein rupture. In addition, the lack of uniformly accepted standards for the performance of adrenal venous sampling contributes to its limited use. Hence, an international panel of experts working at major referral centers was assembled to provide updated advice on how to perform and interpret adrenal venous sampling. To this end, they were asked to use the PICO (Patient or Problem, Intervention, Control or comparison, Outcome) strategy to gather relevant information from the literature and to rely on their own experience. The level of evidence/recommendation was provided according to American Heart Association gradings whenever possible. A consensus was reached on several key issues, including the selection and preparation of the patients for adrenal venous sampling, the procedure for its optimal performance, and the interpretation of its results for diagnostic purposes even in the most challenging

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Evaluation of the Sensitivity and Specificity of¹¹C-Metomidate Positron Emission Tomography (PET)-CT for Lateralizing Aldosterone Secretion by Conn's Adenomas

Abstract: (11)C-metomidate PET-CT is a sensitive and specific noninvasive alternative to AVS in the management of PHA.

Cited by 179 publications

References 32 publications

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

Elevation of Angiotensin-II Type-1-Receptor Autoantibodies Titer in Primary Aldosteronism as a Result of Aldosterone-Producing Adenoma

An Expert Consensus Statement on Use of Adrenal Vein Sampling for the Subtyping of Primary Aldosteronism

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Evaluation of the Sensitivity and Specificity of11C-Metomidate Positron Emission Tomography (PET)-CT for Lateralizing Aldosterone Secretion by Conn's Adenomas

Abstract: (11)C-metomidate PET-CT is a sensitive and specific noninvasive alternative to AVS in the management of PHA.

Cited by 179 publications

References 32 publications

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

Elevation of Angiotensin-II Type-1-Receptor Autoantibodies Titer in Primary Aldosteronism as a Result of Aldosterone-Producing Adenoma

An Expert Consensus Statement on Use of Adrenal Vein Sampling for the Subtyping of Primary Aldosteronism

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Evaluation of the Sensitivity and Specificity of¹¹C-Metomidate Positron Emission Tomography (PET)-CT for Lateralizing Aldosterone Secretion by Conn's Adenomas