[124I]mIBG([124I]mIBG) - _专利_临床

概要

基本信息

药物类型

小分子化药、诊断用放射药物

别名

[124I]meta-Iodobenzylguanidine

靶点-

作用机制

PET imaging(正电子发射断层成像术增强剂)

治疗领域

肿瘤内分泌与代谢疾病其他疾病+ [1]

在研适应症-

非在研适应症

脑癌类癌神经母细胞瘤+ [4]

原研机构

Cancer Research UK

在研机构-

非在研机构

Vancouver Coastal Health

Molecular Insight Pharmaceuticals, Inc.

Cancer Research UK

+ [1]

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

3

项与 [124I]mIBG 相关的临床试验

NCT02279030 / CompletedN/AIIT

Three Dimensional Neuro-cardiac Imaging Using 123I-metaiodobenzylguanidine Single Photon Emission Computed Tomography to Guide Premature Ventricular Contractions Ablations

The purpose of this study is to assess if Single Photon Emission Computed Tomography (SPECT) demonstrating cardiac innervation can be integrated into current electrophysiology voltage mapping system and provide improved guidance for ablation of PVCs.

开始日期2015-06-01

申办/合作机构

University of Maryland Baltimore

[+1]

NCT02043899 / Completed临床1/2期IIT

A Cancer Research UK Phase I/II Study to Compare [124I]Meta-Iodobenzylguanidine (mIBG) Positron Emission Tomography/Computerised Tomography (PET/CT) to [123I]mIBG Imaging in Patients With Metastatic Neuroblastoma

This study aims to show that 3-dimensional PET/CT imaging with a new novel PET tracer (called [124I]mIBG) can detect as many or more sites of neuroblastoma (a type of childhood cancer) compared to the recommended 1-dimensional routine scans (called [123I]mIBG planar scintigraphy).

开始日期2014-02-01

申办/合作机构

Cancer Research UK

NCT02515812 / CompletedN/AIIT

Comparative Study of Cardiac Adrenergic Function Explored by I-123-MIBG and CZT Camera (D-SPECT) Versus Anger Camera in Patients With Heart Failure (ADRECARD)

Cardiological examination constitute one of the major directions in nuclear medicine for detection of myocardial ischemia in patients suspected of coronary disease. In Caen, they constitute 20% of the activity of nuclear medicine. Systolic heart failure (HF) ischemic or nonischemic origin represents a new area of activity of the nuclear cardiology. This is HF stratification study based on cardiac adrenergic function after injection of a tracer: I-123-MIBG. The team Caen nuclear cardiology is one of two teams recognized internationally in the field of evaluating the cardiac sympathetic innervation in cardiomyopathies. Numerous publications from 1992 to the present day have reported encouraging results for the daily use of this tracer in the evaluation of patients with LV dysfunction IC. Recently, interest in using the MIBG has been shown as a prognostic marker of HF in a prospective study of 961 patients. Typically, the camera used was an Anger camera with collimating Nai standard called parallel holes.
The main objective is to validate the measurements of cardiac adrenergic function evaluated by cardiopulmonary mediastinal reports and sympathetic innervation scores VG after injection of I-123-MIBG in 80 patients with heart failure.

开始日期2012-10-01

申办/合作机构

Caen University Hospital

100 项与 [124I]mIBG 相关的临床结果

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100 项与 [124I]mIBG 相关的转化医学

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100 项与 [124I]mIBG 相关的专利（医药）

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181

项与 [124I]mIBG 相关的文献（医药）

2024-09-12·Nature

Substrate binding and inhibition mechanism of norepinephrine transporter

Article

作者: Qi, Yuhan ; Miao, Anran ; Liang, Kai ; Ji, Wenming ; Zhou, Yue ; Wu, Jing-Xiang ; Lai, Lipeng ; Duan, Xinli ; Liu, Jiameng ; Sun, Jixue

Norepinephrine transporter (NET; encoded by SLC6A2) reuptakes the majority of the released noradrenaline back to the presynaptic terminals, thereby affecting the synaptic noradrenaline level¹. Genetic mutations and dysregulation of NET are associated with a spectrum of neurological conditions in humans, making NET an important therapeutic target¹. However, the structure and mechanism of NET remain unclear. Here we provide cryogenic electron microscopy structures of the human NET (hNET) in three functional states-the apo state, and in states bound to the substrate meta-iodobenzylguanidine (MIBG) or the orthosteric inhibitor radafaxine. These structures were captured in an inward-facing conformation, with a tightly sealed extracellular gate and an open intracellular gate. The substrate MIBG binds at the centre of hNET. Radafaxine also occupies the substrate-binding site and might block the structural transition of hNET for inhibition. These structures provide insights into the mechanism of substrate recognition and orthosteric inhibition of hNET.

2024-08-01·Drug Metabolism and Disposition

Cardiac Uptake of the Adrenergic Imaging Agentmeta-Iodobenzylguanidine (mIBG) Is Mediated by Organic Cation Transporter 3 (Oct3)

Article

作者: Vieira, Letícia Salvador ; López Quiñones, Antonio J ; Wang, Joanne

Heart failure (HF) is a chronic disease affecting 1%-2% of the global population.¹²³I-labeled meta-iodobenzylguanidine (mIBG) is US Food and Drug Administration-approved for cardiac imaging and prognosis risk assessment in patients with HF. As a norepinephrine analog, mIBG is believed to be transported into adrenergic nerve terminals by the neuronal norepinephrine transporter (NET) and hence image sympathetic innervation of the myocardium. We previously showed that mIBG is an excellent substrate of organic cation transporter 3 (OCT3), an extraneuronal transporter expressed in cardiomyocytes. Here, we evaluated the in vivo impact of Oct3 on mIBG disposition and tissue distribution using Oct3 knockout mice. Oct3 ^+/+ and Oct3 ^-/- mice were administered with mIBG intravenously, and mIBG plasma pharmacokinetics and tissue exposures were determined. In Oct3 ^+/+ mice, mIBG exhibited extensive accumulation in multiple tissues (heart, salivary gland, liver, and adrenal gland). No difference was observed in overall plasma exposure between Oct3 ^+/+ and Oct3 ^-/- mice. Strikingly, cardiac mIBG was depleted in Oct3 ^-/- mice, resulting in 83% reduction in overall cardiac exposure (AUC_{0-24 h}: 12.7 vs. 2.1 μg × h/g). mIBG tissue exposure (AUC_{0-24 h}) was also reduced by 66%, 36%, and 31% in skeletal muscle, salivary gland, and lung, respectively, in Oct3 ^-/- mice. Our data demonstrated that Oct3 is the primary transporter responsible for cardiac mIBG uptake in vivo and suggested that cardiac mIBG imaging mainly measures OCT3 activity in cardiomyocytes but not NET-mediated uptake in adrenergic nerve endings. Our findings challenge the current paradigm in interpreting cardiac mIBG imaging results and suggest OCT3 as a potential genetic risk marker for HF prognosis. SIGNIFICANCE STATEMENT: ¹²³I-labeled meta-iodobenzylguanidine is used for cardiac imaging and risk assessment in heart failure patients. Contrary to the current belief that meta-iodobenzylguanidine (mIBG) tracks cardiac sympathetic innervation due to its uptake by the neuronal norepinephrine transporter, the authors demonstrated that cardiac mIBG uptake is mediated by the extraneuronal transporter Oct3. Their findings warrant a re-evaluation of the scientific rationale behind cardiac mIBG scan and further suggest organic cation transporter 3 as a risk factor for disease progression in heart failure patients.

2024-04-06·Journal of the Endocrine Society

Anlotinib for Metastatic Progressed Pheochromocytoma and Paraganglioma: A Retrospective Study of Real-World Data

Article

作者: Fu, Jingjing ; Yao, Xiaochen ; Wang, Feng ; Zhang, Chuan ; Wang, Jun ; Yu, Fei ; Shi, Liang ; Song, Jieping ; Zhang, Pengjun ; Tian, Rui ; Ni, Yudan

AbstractIntroductionPheochromocytomas (PCC) and paragangliomas (PGL) (collectively PPGL) are a type of rare hypervascular neuroendocrine tumors that are very challenging to treat. This study aimed to determine the efficacy and safety of the multi-tyrosine kinase inhibitor anlotinib for the treatment of locally advanced or metastatic (LA/M) PPGL.MethodsA total of 37 eligible patients with unresectable or progressive LA/M PPGL were enrolled. Of them, 27 patients received anlotinib alone (n = 19) or in combination (n = 8) with radionuclide therapies, including peptide receptor radionuclide therapy (PRRT) and iodine 131 meta-iodobenzylguanidine (131I-MIBG). The primary endpoints included objective response rate (ORR), defined as partial response (PR) or complete response (CR), and disease-control rate, defined as PR, CR, or stable disease (SD). The secondary endpoints were progression-free survival (PFS), duration of response, and drug safety.ResultsIn the efficacy evaluation for all 27 patients, the ORR was 44.44% (95% CI: 24.4%-64.5%) and disease-control rate was 96.29% (95% CI: 88.7%-100%). Twelve cases (44.44%) achieved PR, 14 (51.85%) SD. The median PFS was 25.2 months (95% CI: 17.2 months to not reached). PFS was shorter in the anlotinib monotherapy group than in the group receiving anlotinib in combination with radionuclide therapy (P = .2). There were no serious treatment-related AEs.ConclusionAnlotinib monotherapy or in combination with radionuclide therapies shows promising efficacy and safety for the treatment of LA/M PCC and PGL. Multi-tyrosine kinase inhibitors might represent a novel therapeutic strategy for patients with PPGL; however, large-scale prospective randomized, blinded, controlled clinical research studies are required.

100 项与 [124I]mIBG 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
脑癌	临床3期	英国	Cancer Research UK	2014-02-28
神经内分泌肿瘤	临床3期	美国	Molecular Insight Pharmaceuticals, Inc.	2013-04-09
神经内分泌肿瘤	临床3期	美国	Jubilant Draximage, Inc.初创企业	2013-04-09
甲状腺癌	临床3期	美国	Jubilant Draximage, Inc.初创企业	2013-04-09
甲状腺癌	临床3期	美国	Molecular Insight Pharmaceuticals, Inc.	2013-04-09
类癌	临床3期	加拿大	Vancouver Coastal Health	-
神经母细胞瘤	临床3期	加拿大	Vancouver Coastal Health	-
神经母细胞瘤	临床3期	加拿大	Vancouver Coastal Health	-
嗜铬细胞瘤	临床3期	加拿大	Vancouver Coastal Health	-
甲状腺髓样癌	临床3期	加拿大	Vancouver Coastal Health	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02043899 (CTgov)	临床1/2期	神经母细胞瘤	36	[124I]meta-Iodobenzylguanidine	製蓋簾選範淵鬱積獵廠(築選淵製襯願選顧壓醖) = 構糧範壓築遞網願顧淵鏇顧獵簾齋積築鏇簾構 (製壓顧範鹽顧範憲艱齋, 構鏇獵鏇夢蓋淵蓋築餘 ~ 網壓範鬱範艱蓋簾遞夢) 更多	-	2021-06-21