Functional Characterization of Adrenal Lesions Using [123I]IMTO-SPECT/CT

Hahner, Stefanie; Kreißl, Michael C.; Fassnacht, Martin; Haenscheid, Heribert; Böck, Stefanie; Verburg, Frederik A.; Knoedler, Pascal; Lang, Katharina; Reiners, Christoph; Buck, Andreas K.; Allolio, Bruno; Schirbel, Andreas

doi:10.1210/jc.2012-3045

Cited by 47 publications

(29 citation statements)

References 25 publications

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“…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. However, it is unclear whether this also holds true for adrenocortical adenoma cells because ACTH (adrenocorticotropic hormone) receptor expression is low in NFAs.…”

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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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: 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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Section: Future Directions In Diagnosing Accmentioning

confidence: 95%

“…IMTO does show uptake in metastasis of ACC (Hahner et al 2013. In two studies, sensitivity and specificity for characterization of adrenal lesions was 89% and 85%, and 38% and 100% respectively (Hahner et al 2013. Early results suggest that proton MR spectroscopy may be useful in discriminating pheochromocytomas and adrenal adenomas from adrenal metastases and ACC.…”

Section: Future Directions In Diagnosing Accmentioning

confidence: 99%

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Creemers¹,

Hofland²,

Korpershoek³

et al. 2015

Endocrine-Related Cancer

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Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Discrimination between ACCs and adrenocortical adenomas (ACAs) remains challenging, with the current gold standard being the Weiss score, consisting of several histopathological characteristics. However, new markers like Ki67, a marker for proliferation, and the staining of reticulins are promising not only as it comes to identifying malignancy but also as prognostic markers in patients with ACC. Currently, surgery is still the only curative treatment for ACC. Mitotane, an adrenolytic drug, is used in the adjuvant setting and in case of metastatic or advanced disease. Patients with progressive disease are frequently treated with mitotane, alone or in combination with etoposide, doxorubicine and cisplatin. Radiotherapy is indicated in selected cases. The low response rates and high toxicity of the systemic therapies emphasize the need for markers that enable the identification of responders and non-responders. Consequently, research is focusing on predictive factors varying from the expression of DNA repair genes to clinical patient characteristics. Subgroups of ACC with different prognosis have been identified based on transcriptome characteristics. As a conclusion from large molecular studies, ACCs appear to harbor many abnormalities compared to ACAs. Altered pathways driving ACC pathogenesis include the IGF, TP53 and the Wnt signaling pathway, allowing these as new potential targets for medical therapy. However, despite efforts in preclinical and clinical studies investigating efficacy of targeting these pathways, most novel therapies appear to be effective in only a subset of patients with ACC. New treatment concepts are therefore urgently needed.

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“…[123I]IMTO for single photon emission computed tomography (SPECT) and planar scintigraphy has proved a valuable alternative to PET imaging with a sensitivity of 89 % and a specificity of 85 % for differentiating adrenocortical tumors from lesions of non-adrenocortical origin [47]. A recent report in a larger series of patients with adrenocortical cancer has shown that only a subset of ACCs is clearly positive by SPECT/CT iodometomidate imaging [48].…”

Section: Pet-pet/ctmentioning

confidence: 99%

Management of adrenocortical carcinoma: a consensus statement of the Italian Society of Endocrinology (SIE)

Stigliano

Chiodini

Giordano

et al. 2015

J Endocrinol Invest

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Functional Characterization of Adrenal Lesions Using [123I]IMTO-SPECT/CT

Cited by 47 publications

References 25 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

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Management of adrenocortical carcinoma: a consensus statement of the Italian Society of Endocrinology (SIE)

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