Adrenal masses are highly prevalent and detected with high frequency by conventional imaging. Conventional imaging often fails to rule out a malignant lesion. Accordingly, most hormonally inactive adrenal masses removed by surgery are benign adenomas for which surgical removal is unnecessary and poses an avoidable risk to the patients. We hypothesize that the combination of FDG-PET and 123I-Iodometomidate imaging has the potential to noninvasively identify benign adrenocortical adenomas with high accuracy, thereby avoiding unnecessary surgery. Uptake of 123I-Iodometomidate by the adrenal mass demonstrates the presence of CYP 11B enzymes which specifically bind metomidate with high avidity establishing the adrenocortical origin of the lesion, while low uptake of FDG-PET in an adrenocortical lesion establishes its benign nature and excludes the presence of adrenocortical cancer (ACC). The proposed trial will assess the sensitivity, specificity, positive and negative predictive value of the combined imaging for the diagnosis of adrenocortical adenoma. A secondary focus is on the performance of the combined test for differentiating ACC from non-ACC lesions. We expect that the results of our trial will help to greatly reduce the need for surgery in hormonally inactive adrenal masses.

开始日期2015-08-01

申办/合作机构

Wuerzburg University Hospital

[+14]

NCT00454103 / Completed临床1/2期

Evaluation of 123I-Iodometomidate for Adrenal Scintigraphy

The improvement of conventional imaging techniques has led to an increased detection rate of different adrenal tumors. Since those tumors can belong to a variety of entities the therapeutic consequences also show considerable variation. In order to definitely determine the type of tumor, invasive procedures like CT guided biopsies are often required, which could be avoided by a tumor specific imaging method. The presently available scintigraphic procedures are either time consuming and lead to high radiation exposure or are technically demanding. The steroidogenic enzymes CYP11B1 (11ß-hydroxylase)and CYP11B2 (aldosterone synthase)are expressed exclusively in the adrenal cortex and therefore represent suitable targets for a specific imaging technique. In our project we evaluate 123I-Iodometomidate which binds to both CYP11B enzymes as radiotracer for adrenal scintigraphy.

开始日期2007-03-01

申办/合作机构

Julius-Maximilians-Universität Würzburg

100 项与 [123I]-Iodometomidate 相关的临床结果

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100 项与 [123I]-Iodometomidate 相关的转化医学

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100 项与 [123I]-Iodometomidate 相关的专利（医药）

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项与 [123I]-Iodometomidate 相关的文献（医药）

2013-07-01·The Journal of Clinical Endocrinology & Metabolism2区 · 医学

[123I]Iodometomidate Imaging in Adrenocortical Carcinoma

2区 · 医学

Article

作者: Reiners, Christoph ; Schirbel, Andreas ; Saeger, Wolfgang ; Kreissl, Michael C. ; Allolio, Bruno ; Haenscheid, Heribert ; Bock, Stefanie ; Buck, Andreas K. ; Knoedler, Pascal ; Hahner, Stefanie ; Verburg, Frederik A. ; Fassnacht, Martin

CONTEXTImaging with [¹²³I]iodometomidate ([¹²³I]IMTO) has been shown to diagnose adrenocortical lesions with high sensitivity and specificity.OBJECTIVEOur objective was to evaluate the clinical utility of [¹²³I]IMTO imaging in adrenocortical carcinoma (ACC).DESIGNWe conducted a prospective monocentric diagnostic study and a prospective case series at a single tertiary referral center.PATIENTS AND INTERVENTIONSFifty-eight patients with histologically confirmed ACC, all European Network for the Study of Adrenal Tumors stage IV (with distant metastases), received 185 MBq [¹²³I]IMTO. Sequential planar whole-body scans until 24 hours post injection and single photon emission computed tomography/computed tomography (SPECT/CT) hybrid imaging 4 to 6 hours post injection were performed.MAIN OUTCOME MEASURESOutcome measures included uptake of [¹²³I]IMTO in ACC lesions, sensitivity and specificity of [¹²³I]IMTO imaging compared with conventional imaging, and number of patients eligible for [¹³¹I]IMTO therapy.RESULTSOf 430 lesions detected by conventional imaging, 30% showed strong, 8% moderate, and 62% no tracer accumulation. [¹²³I]IMTO detected both primary and metastatic lesions of ACC. However, a substantial percentage of lesions failed to show [¹²³I]IMTO uptake. The overall sensitivity and specificity values were 38% and 100%, respectively. Thirty-four patients (59%) had at least 1 [¹²³I]IMTO-positive lesion. Cortisol and aldosterone secretion by ACC was positively correlated to [¹²³I]IMTO uptake (P = .01); cytotoxic chemotherapy and mitotane treatment presumably did not influence tracer uptake. Twenty-one patients (36.2%) had radiotracer uptake in all lesions ≥ 2 cm and therefore were potential candidates for targeted systemic radiotherapy with [¹³¹I]IMTO.CONCLUSIONAbout one-third of patients with ACC show specific retention of [¹²³I]IMTO in metastatic lesions. This study provides support for the conduct of a prospective trial to determine whether the first molecular informed therapy using [¹³¹I]IMTO will be of value to patients with metastatic ACC.

2012-03-01·The Journal of Clinical Endocrinology & Metabolism2区 · 医学

[131I]Iodometomidate for Targeted Radionuclide Therapy of Advanced Adrenocortical Carcinoma

2区 · 医学

Article

作者: Haenscheid, Heribert ; Reiners, Christoph ; Kreissl, Michael C. ; Lang, Katharina ; Allolio, Bruno ; Hahner, Stefanie ; Buck, Andreas K. ; Knoedler, Pascal ; Schirbel, Andreas ; Fassnacht, Martin

CONTEXTIn advanced adrenocortical carcinoma (ACC), many patients have progressive disease despite standard treatment, indicating a need for new treatment options. We have shown high and specific retention of [123I]metomidate ([123I]IMTO) in ACC lesions, suggesting that labeling of metomidate with 131I offers targeted radionuclide therapy for advanced ACC.OBJECTIVESafety and efficacy of radionuclide therapy with [131I]IMTO in advanced ACC.DESIGN/SETTINGThis monocentric case series comprised 19 treatments in 11 patients with nonresectable ACC.PATIENTS AND INTERVENTIONBetween 2007 and 2010, patients with advanced ACC not amenable to radical surgery and exhibiting high uptake of [123I]IMTO in their tumor lesions were offered treatment with [131I]IMTO (1.6-20 GBq in one to three cycles of [131I]IMTO).MAIN OUTCOME MEASURETumor response was assessed according to response evaluation criteria in solid tumors (RECIST version 1.1) criteria, and side effects were assessed by Common Toxicity Criteria (version 4.0).RESULTSBest response was classified as partial response in one case with a change in target lesions of -51% from baseline, as stable disease in five patients, and as progressive disease in four patients. One patient died 11 d after treatment with [131I]IMTO unrelated to radionuclide therapy. In patients responding to treatment, median progression-free survival was 14 months (range, 5-33) with ongoing disease stabilization in three patients at last follow-up. Treatment was well tolerated, but transient bone marrow depression was observed. Adrenal insufficiency developed in two patients.CONCLUSIONSRadionuclide therapy with [131I]IMTO is a promising treatment option for selected patients with ACC, deserving evaluation in prospective clinical trials.

2011-11-01·Journal of Psychopharmacology3区 · 医学

Does intravenous Δ9-tetrahydrocannabinol increase dopamine release? A SPET study

3区 · 医学

Article

作者: Kapur, Shitij ; Pilowsky, Lyn S ; Powell, John ; Dickson, John C ; Murray, Robin M ; Ell, Peter J ; Vuletic, D ; Brenneisen, Rudolf ; Morrison, Paul D ; Barkus, Emma ; Holt, David W

Intravenous (IV) Δ9-tetrahydrocannabinol (THC) induces transient psychotic symptoms in healthy subjects and in schizophrenic patients, but the psychotomimetic mechanism is unknown. One possibility is that THC stimulates dopamine (DA) release in the striatum. In this study we tested whether IV THC led to an increase in striatal DA release compared to placebo. We also investigated whether DA release and positive psychotic symptoms were related. Eleven healthy male volunteers completed two 123I-iodobenzamide ([123I]IBZM) single photon emission tomography (SPET) sessions and received IV THC (2.5 mg) or placebo in a randomized counterbalanced order, under double-blind conditions. Analysable data were obtained from nine participants. The Positive and Negative Syndrome Scale (PANSS) was used to rate psychotomimetic effects. Striatal binding index values were calculated using the occipital cortex as a reference region. Both the PANSS positive and general symptoms increased significantly at 30 min following IV THC. There were no significant differences in binding index in the caudate or putamen under THC compared to placebo conditions. Positive psychotic symptoms and DA release were unrelated. THC did not lead to a significant increase in DA release even though the dose was sufficient for participants to have psychotic symptoms. These findings do not support a central role for striatal DA in THC-elicited psychosis.

100 项与 [123I]-Iodometomidate 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
肾上腺肿瘤	临床3期	德国	Wuerzburg University Hospital	2015-08-01
肾上腺皮质癌	临床3期	德国	Julius-Maximilians-Universität Würzburg	2007-03-01