Delving into the Latest Updates on [124I]mIBG with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

[124I]meta-Iodobenzylguanidine

Target-

Mechanism

PET imaging(Positron-emission tomography enhancers)

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseOther Diseases+ [1]

Active Indication-

Inactive Indication

Brain CancerCarcinoid TumorNeuroblastoma+ [4]

Originator Organization

Cancer Research UK

Active Organization-

Inactive Organization

Vancouver Coastal Health

Molecular Insight Pharmaceuticals, Inc.

Cancer Research UK

+ [1]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

Login to view timeline

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.

Start Date01 Oct 2012

Sponsor / Collaborator

Caen University Hospital

100 Clinical Results associated with [124I]mIBG

Login to view more data

100 Translational Medicine associated with [124I]mIBG

Login to view more data

100 Patents (Medical) associated with [124I]mIBG

Login to view more data

179

Literatures (Medical) associated with [124I]mIBG

12 Sep 2024·Nature

Substrate binding and inhibition mechanism of norepinephrine transporter

Article

Author: 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.

01 Aug 2024·Drug Metabolism and Disposition

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

Article

Author: 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.

06 Apr 2024·Journal of the Endocrine Society

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

Article

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

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 Deals associated with [124I]mIBG

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Brain Cancer	Phase 3	GB	Cancer Research UK	28 Feb 2014
Neuroendocrine Tumors	Phase 3	US	Molecular Insight Pharmaceuticals, Inc.	09 Apr 2013
Neuroendocrine Tumors	Phase 3	US	Jubilant Draximage, Inc.Startup	09 Apr 2013
Thyroid Cancer	Phase 3	US	Jubilant Draximage, Inc.Startup	09 Apr 2013
Thyroid Cancer	Phase 3	US	Molecular Insight Pharmaceuticals, Inc.	09 Apr 2013
Carcinoid Tumor	Phase 3	CA	Vancouver Coastal Health	-
Neuroblastoma	Phase 3	CA	Vancouver Coastal Health	-
Neuroblastoma	Phase 3	CA	Vancouver Coastal Health	-
Pheochromocytoma	Phase 3	CA	Vancouver Coastal Health	-
Thyroid Cancer, Medullary	Phase 3	CA	Vancouver Coastal Health	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02043899 (CTgov)	Phase 1/2	Neuroblastoma	36	[124I]meta-Iodobenzylguanidine	ielsuthywq(dxfnmzynce) = vclixdemna uevesxmetk (cbpkmltooh, mwzlzmnzdz - lhdxhkvvhm) View more	-	21 Jun 2021