碘[123I]苄胍(Iobenguane I-123) - 在研适应症：心脏衰竭，神经母细胞瘤，嗜铬细胞瘤_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

123I-Iobenguane、3-Iodobenzylguanidine (123I)、3-Iodobenzylguanidine (123I) Injection

+ [7]

靶点-

作用机制

SPECT(单光子发射计算机断层成像术增强剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

PDRadiopharma, Inc.GE Healthcare, Inc.

非在研机构

GE Healthcare Holdings, Inc.

最高研发阶段批准上市

首次获批日期

日本 (1992-10-02),

诊断试剂

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

登录后查看时间轴

结构

分子式C8H12IN3O4S

InChIKeyNMHJRGCKGFRFAQ-JZXKKTDRSA-N

CAS号139755-80-9

关联

19

项与碘[123I]苄胍相关的临床试验

DRKS00023773 / CompletedN/AIIT

Long Term Cardiac Risk in Recovered COVID-19 Patients Evaluated by 123I-mIBG - COVID-19 HERZ MIBG SPECT

开始日期2021-09-21

申办/合作机构-

NL-OMON48497 / Suspended临床4期IIT

(123I-mIBG And Defibrillation for Atrial Fibrillation): Enhanced sympathetic activity as a mechanism of Atrial Fibrillation recurrence - MAD-AF

开始日期2020-12-31

申办/合作机构-

JPRN-UMIN000025045 / CompletedIIT

Prospective study of I-131 3-iodobenzylguanidine radiotherapy for high-risk neuroblastoma; in accordance with the Japanese Advanced Medical Care B program for the anticancer drug with high medical needs. - Prospective study of I-131 3-iodobenzylguanidine radiotherapy for high-risk neuroblastoma; in accordance with the Japanese Advanced Medical Care B program for the anticancer drug with high medical needs.

开始日期2017-07-01

申办/合作机构

Kanazawa University

100 项与碘[123I]苄胍相关的临床结果

登录后查看更多信息

100 项与碘[123I]苄胍相关的转化医学

登录后查看更多信息

100 项与碘[123I]苄胍相关的专利（医药）

登录后查看更多信息

258

项与碘[123I]苄胍相关的文献（医药）

2024-10-01·ANNALS OF NUCLEAR MEDICINE

Sympathetic 123I-metaiodobenzylguanidine index for Lewy body disease: probability-based diagnosis and identifying patients exempt from late imaging

Article

作者: Komatsu, Junji ; Wakabayashi, Hiroshi ; Matsumura, Takeshi ; Kinuya, Seigo ; Ono, Kenjiro ; Nakajima, Kenichi

Abstract:

Objective:

We aimed to establish a practical diagnostic index for Lewy body diseases (LBD), such as Parkinson’s disease and dementia, with Lewy bodies in outpatient settings and criteria for exempting patients from late imaging.

Methods:

We acquired early and late 123I-metaiodobenzylguanidine (MIBG) images from 108 consecutive patients with suspected LBD and standardized heart-to-mediastinum (H/M) ratios for collimator conditions. Exclusions included young-onset Parkinson’s disease (age < 50 years) and genetic transthyretin-type amyloidosis. We developed logistic models incorporating H/M ratios with or without age (n = 92). The sympathetic MIBG index for LBD (SMILe index), categorized LBD likelihood from 0 (lowest) to 1 (highest). Diagnostic accuracy was assessed as the area under the receiver operating characteristic (ROC) curve (AUC). The characteristics of the new index were compared with H/M ratios. The need for late imaging was explored using the SMILe index.

Results:

Early or late SMILe indexes using a single H/M ratio variable discriminated LBD from non-LBD. The AUC values for early and late SMILe indexes were 0.880 and 0.894 (p < 0.0001 for both), identical to those for early and late H/M ratios. The sensitivity and the specificity of early SMILe indexes with a 0.5 threshold were 76% and 90%, achieving accuracy of accuracy 86%. Similarly, the late SMILe index demonstrated a sensitivity of 76% and specificity of 87%, with an accuracy of 84%. Early SMILe indexes < 0.3 or > 0.7 (representing 84% patients) indicated a diagnosis without a late MIBG study.

Conclusion:

The 123I-MIBG-derived SMILe indexes provide likelihood of LBD, and those with a 50% threshold demonstrated optimal diagnostic accuracy for LBD. The index values of either < 0.3 or > 0.7 accurately selected patients who do not need late imaging.

2024-06-25·JOURNAL OF ALZHEIMERS DISEASE

Diagnostic Sensitivity and Symptomatic Relevance of Dopamine Transporter Imaging and Myocardial Sympathetic Scintigraphy in Patients with Dementia with Lewy Bodies

Article

作者: Kitayama, Yoshihisa ; Tamura, Mitsuyoshi ; Uno, Takashi ; Hirano, Shigeki ; Yokota, Hajime ; Koizumi, Yume ; Ishikawa, Ai ; Kashiwado, Kouichi ; Mukai, Hiroki ; Iimori, Takashi ; Kuwabara, Satoshi ; Izumi, Michiko ; Horikoshi, Takuro ; Tang, Zhihui ; Yamagishi, Kosuke

Background: Dementia with Lewy bodies (DLB) presents with various symptoms, posing challenges for early diagnosis challenging. Dopamine transporter (123I-FP-CIT) single-photon emission tomography (SPECT) and 123I-meta-iodobenzylguanidine (123I-MIBG) imaging are crucial diagnostic biomarkers. Hypothesis about body- and brain-first subtypes of DLB indicate that some DLB may show normal 123I-FP-CIT or 123I-MIBG results; but the characteristic expression of these two subtypes remains unclear. Objective: This study aimed to evaluate the diagnostic sensitivity of 123I-FP-CIT and 123I-MIBG imaging alone, combined in patients with DLB and explore symptoms associated with the abnormal imaging results. Methods: Demographic data, clinical status, and imaging results were retrospectively collected from patients diagnosed with possible DLB. Both images were quantified using semi-automated software, and the sensitivity of each imaging modality and their combination was calculated. Demographic data, cognition, and motor and non-motor symptoms were compared among the subgroups based on the imaging results. Symptoms related to each imaging abnormality were examined using binomial logistic regression analyses. Results: Among 114 patients with DLB, 80 underwent 123I-FP-CIT SPECT (sensitivity: 80.3%), 83 underwent 123I-MIBG imaging (68.2%), and 66 both (sensitivity of either abnormal result: 93.9%). Visual hallucinations differed among the four subgroups based on imaging results. Additionally, nocturia and orthostatic hypotension differed between abnormal and normal 123I-MIBG images. Conclusions: Overall, 123I-FP-CIT SPECT was slightly higher sensitivity than 123I-MIBG imaging, with combined imaging increasing diagnostic sensitivity. Normal results of a single imaging test may not refute DLB. Autonomic symptoms may lead to abnormal 123I-MIBG scintigraphy findings indicating body-first subtype of patients with DLB.

2024-05-01·Clinical nuclear medicine

A Rare Case of Abnormal Diffuse Brain Uptake on an 123I MIBG Scan in a Patient With High-Risk Neuroblastoma

Article

作者: Sadic, Murat ; Basavalingu, Deepashri ; Parisi, Marguerite T ; Cheeney, Safia

Abstract:

123I-meta-iodobenzylguanidine (123I-MIBG) is extensively used for initial staging and response evaluation in children with neuroblastoma. Physiological uptake of 123I-MIBG occurs in the salivary glands, liver, adrenal gland, myocardium, bowel, and thyroid gland. 123I-MIBG cannot cross an intact blood-brain barrier. We present the rare case of a 3-year-old boy with neuroblastoma and meningeal metastases who underwent an 123I-MIBG scan for disease restaging that showed abnormal brain uptake. Abnormal MIBG uptake in the brain can occur if there is disruption of the blood-brain barrier either secondary to metastases or after damage to blood-brain barrier.

1

项与碘[123I]苄胍相关的新闻（医药）

2024-08-15

·微信

Nature | 吴惊香课题组揭示去甲肾上腺素转运蛋白底物结合和抑制的结构机制

引言去甲肾上腺素（NA）是一种重要的神经递质，在调节大脑和身体的活跃状态中起着至关重要的作用。NA系统的功能障碍可导致多种疾病的发生，包括交感神经过度活化、注意缺陷多动障碍（ADHD）、自主神经功能衰竭、应激、抑郁和嗜铬细胞瘤等。NET（去甲肾上腺素转运体）能够将释放到突触间隙中的NA再摄取回突触前端，进而控制NA信号的强度和持续时间。NET异常与诸多疾病相关，是重要的成像及治疗靶标。目前，NET底物类似物被广泛用来诊断和治疗多种神经内分泌肿瘤、以及心脏病和帕金森病的诊断；各类NET抑制剂也在临床上发挥治疗ADHD、神经退行性疾病、药物滥用、焦虑和抑郁等疾病的作用。因此，阐明NET的底物转运机制以及药物抑制机制是该领域结构药理学的核心问题。 2024年8月14日，中国医学科学院药物研究所天然药物及核药基础与新药创制全国重点实验室吴惊香课题组在Nature在线发表题为Substrate binding and inhibition mechanism of norepinephrine transporter的研究论文。该研究解析了关键的神经系统疾病靶标——人源去甲肾上腺素转运体（Norepinephrine transporter, hNET）三个不同功能状态下的高分辨率结构，揭示了其底物识别及抑制剂抑制作用机制，为以NET为靶标的药物研发提供了结构基础。为解决hNET小分子量蛋白结构解析困难的问题，研究人员在不影响蛋白表达和功能的基础上，创新性地引入PA标签系统，最终解析了hNET在无底物结合状态（Apo）, 底物间碘苄胍（MIBG）结合和 (S,S)-羟基安非他酮（radafaxine）结合的三种不同功能状态的三维结构，分辨率在2.8-3.0埃之间。 hNET属于单胺类神经递质转运蛋白（Monoamine transporters; MATs），由12个跨膜螺旋组成，其中跨膜螺旋1-5和6-10形成一个结构类似的倒置重复，是转运底物的结构核心。此外，研究团队还观察到hNET与其它已解析的MATs家族成员结构不同，hNET胞内羧基端是由三个螺旋组成，与跨膜区有广泛的相互作用，显示出其羧基端的功能重要性。作者们发现无底物结合状态的hNET处于向内开口的构象，胞外门控处的氨基酸形成了多样的电荷互作和氢键网络，使得胞外门控处于紧密的关闭状态。 MIBG是底物NA的一种合成胍乙啶类似物，能够被NET摄取存储于突触前端。放射性核素标记的[123I]MIBG是交感神经系统放射性成像的金标准，能诊断和治疗多种神经内分泌肿瘤，比如儿童“癌症之王”——神经母细胞瘤。研究人员发现底物MIBG-结合状态的hNET同样是胞外门控紧闭且胞内门控打开，处于向内开口的构象，MIBG稳定地结合在底物结合口袋中心，通过氢键以及疏水作用等与hNET的A, B, C三个亚位点的氨基酸发生广泛的相互作用。由于NA和MIBG在结构和功能上的类似性，作者们推测NA也是以类似MIBG的方式结合在hNET的中心结合口袋上，这些信息为理解hNET的底物结合机制提供了结构基础。 Radafaxine是安非他酮（Bupropion）的一种活性代谢物，安非他酮可用来帮助戒烟和作为非典型抗抑郁药，用于治疗重度抑郁症障碍，是近几年来最常见的处方药之一。研究人员发现radafaxine-结合状态的hNET同样处于向内开口的构象，radafaxine占据了hNET的底物结合位点，通过与周围氨基酸形成π-π, 电子-π，氢键以及疏水作用等产生稳定的结合。Radafaxine完全占据了底物结合位点，阻止底物的进入，表明其是以正构抑制剂的形式发挥作用。与MAT家族已解析的其它构象的结构比较，radafaxine与外向开口的构象是有空间位阻的，作者推测radafaxine稳定hNET始终保持在内向开口构象，抑制其向向外开口构象转变，进而使hNET丧失转运活性。图 hNET三种功能状态代表性结构、特征以及MIBG和radafaxine结合位点比较（Credit: Nature）综上，作者通过冷冻电镜对hNET三个不同功能状态的结构进行解析，发现hNET的整体结构类似于MATs家族成员；MIBG-结合的结构展示了hNET底物结合口袋的独特性，保证了其对NA特异性的摄取；radafaxine通过占据底物结合位点并可能阻止其构象变化来抑制hNET。这些信息为进一步理解hNET的机制和动态变化提供了坚实的基础，为以hNET为靶标的药物设计提供了关键信息。值得一提的是，近期有三项研究分别独立解析了NET结合不同配体，在不同构象下的结构【1-3】，这些研究各有特点，相得益彰，和本研究一起为对NET的底物识别、转运机制以及结构药理机制的理解提供了基础，为以 NET为靶标的药物治疗和设计提供了重要参考。参考文献 1 Hu, T. et al. Transport and inhibition mechanisms of the human noradrenaline transporter. Nature, doi:10.1038/s41586-024-07638-z (2024). 2 Tan, J. et al. Molecular basis of human noradrenaline transporter reuptake and inhibition. Nature, doi:10.1038/s41586-024-07719-z (2024). 3 Zhang, H. et al. Dimerization and antidepressant recognition at noradrenaline transporter. Nature 630, 247-254, doi:10.1038/s41586-024-07437-6 (2024). https://www-nature-com.libproxy1.nus.edu.sg/articles/s41586-024-07810-5 责编|探索君排版|探索君文章来源|“BioArt” End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

生物类似药

100 项与碘[123I]苄胍相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	V09	DB09546

研发状态

批准上市

10 条最早获批的记录,

登录

后查看更多信息

适应症	国家/地区	公司	日期
心脏衰竭	美国	GE Healthcare, Inc.	2013-03-20
神经母细胞瘤	美国	GE Healthcare, Inc.	2008-09-19
嗜铬细胞瘤	美国	GE Healthcare, Inc.	2008-09-19
诊断试剂	日本	PDRadiopharma, Inc.	1992-10-02

未上市

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
冠心病	临床3期	加拿大	GE Healthcare Holdings, Inc.	2013-12-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


SNMMI2024	N/A	副神经节瘤 \| 嗜铬细胞瘤	-	Single-dose MIBG therapy	艱膚願網鑰膚鑰廠鏇窪(獵壓糧鏇顧膚醖築鹹膚) = 繭範製醖鏇觸壓鏇鏇構鑰築網襯網築鬱願構憲 (積築蓋築夢膚糧選選餘 ) 更多	-	2024-06-09
				Multiple-dose MIBG therapy	艱膚願網鑰膚鑰廠鏇窪(獵壓糧鏇顧膚醖築鹹膚) = 簾齋醖糧觸蓋鑰餘製構鑰築網襯網築鬱願構憲 (積築蓋築夢膚糧選選餘 ) 更多
SNMMI2023	N/A	嗜铬细胞瘤	-	123I-meta-iodobenzylguanidine	醖顧衊簾餘衊構繭蓋選(獵選觸齋壓網鑰齋獵襯) = At each time point, the trends of the biodistribution of ¹²³I-MIBG and ²¹¹At-MABG were almost similar in pheochromocytoma xenograft mice 簾積製淵衊簾鹹選襯鏇 (齋鏇膚繭鹽鑰蓋製範構 )	-	2023-08-28
				211At-astato-benzylguanidine
SNMMI2023	N/A	神经母细胞瘤	-	[18F]mFBG Long Axial Field Of View (LAFOV) PET/CT	廠衊襯顧膚膚範顧觸鹽(顧網淵衊鹹獵製鹽願築) = 構網鹹積衊襯築積窪願夢膚蓋築醖蓋憲憲構築 (網鏇築蓋糧醖壓壓鹹繭, 2.6)	-	2023-08-28
				[123I]mIBG scintigraphy with single-photon emission computed tomography-CT (SPECT/CT)	廠衊襯顧膚膚範顧觸鹽(顧網淵衊鹹獵製鹽願築) = 衊餘鏇範憲範襯餘壓憲夢膚蓋築醖蓋憲憲構築 (網鏇築蓋糧醖壓壓鹹繭, 16.3)
SNMMI2020	N/A	-	-	123I-MIBG	遞壓範鏇襯襯鬱觸淵襯(製淵鬱願鹹顧顧鹽淵築) = 廠築齋醖襯糧餘淵鏇廠築艱觸襯範顧鹽淵築網 (壓鑰餘構鹽衊顧積襯構, 8.86) 更多	-	2020-05-15
				211At-MABG	遞壓範鏇襯襯鬱觸淵襯(製淵鬱願鹹顧顧鹽淵築) = 襯構遞製獵夢膚築醖積築艱觸襯範顧鹽淵築網 (壓鑰餘構鹽衊顧積襯構, 4.79) 更多
NCT02656329 (ADMIRE-ICD, CTgov)	临床3期	心力衰竭NYHA III级	395	Thyroid blocking+Iobenguane I -123 Injection (AdreView™)	築艱簾築艱壓簾壓餘衊(觸廠鹹鹹糧憲構網繭鹽) = 鬱壓築網醖壓鹹蓋壓夢觸鬱鏇鬱範鏇窪獵廠鑰 (簾醖鑰齋鏇衊艱憲衊遞, 壓顧夢廠願餘願簾醖蓋 ~ 獵選積膚獵鹽積鑰願餘) 更多	-	2019-05-22
				Implantable Cardioverter Defibrillator+Iobenguane I -123 Injection (Standard of Care)	築艱簾築艱壓簾壓餘衊(觸廠鹹鹹糧憲構網繭鹽) = 築簾簾鹹網簾繭襯鏇壓觸鬱鏇鬱範鏇窪獵廠鑰 (簾醖鑰齋鏇衊艱憲衊遞, 廠醖鑰艱製構齋獵淵構 ~ 糧鹽衊遞範蓋鬱鹽簾夢) 更多
SNMMI2017	N/A	高风险神经母细胞瘤 123I-MIBG	76	123I-MIBG (New detailed semi-quantitative scoring system)	憲憲構蓋鏇廠鹹齋製艱(衊範膚鑰鏇範簾夢積齋) = 鑰壓築顧獵積鑰築襯鬱艱窪醖憲鹹窪憲願艱淵 (齋鹽積醖構襯壓廠膚鏇 )	积极	2017-05-24
ESC2016	N/A	ST段抬高心肌梗死	94	123I-MIBG SPECT	網獵鹹夢壓鏇壓觸蓋夢(鬱壓艱鬱顧壓積繭繭窪) = 襯積襯範蓋鹹願構積餘衊繭鹹鬱積鹽築範範鬱 (襯願憲淵鹹齋艱壓構選 )	-	2016-08-30
SNMMI2015	N/A	-	-	123I-mIBG	簾簾鹽遞蓋廠窪繭鹽遞(艱觸醖顧窪積鹹顧鏇構) = 觸鬱繭衊淵憲鹹繭範獵遞鏇獵夢鬱齋鹽築蓋衊 (獵積鹽艱鹹願鹹衊鏇鹹, 4.3)	-	2015-05-15
SNMMI2015	N/A	甲状腺疾病	-	123I-MIBG (CHF patients)	願蓋獵夢壓糧蓋窪築鏇(廠壓簾鹽選製願觸壓積) = 餘鬱齋夢憲膚築淵蓋淵構糧夢願餘遞齋齋鏇壓 (築築願齋鏇衊構網餘夢, 7.2) 更多	-	2015-05-15
				123I-MIBG (PD-MD patients)	願蓋獵夢壓糧蓋窪築鏇(廠壓簾鹽選製願觸壓積) = 鹹襯膚鏇觸簾選築鏇獵構糧夢願餘遞齋齋鏇壓 (築築願齋鏇衊構網餘夢, 8.1)
SNMMI2014	N/A	心律失常	-	123I-mIBG SPECT	觸糧鏇積襯蓋獵選衊鏇(築鹹簾鑰齋鬱範蓋餘簾) = 顧夢鏇齋膚窪築遞選選糧遞網繭糧鑰憲艱餘醖 (壓膚選鬱積築築襯襯網 )	-	2014-11-05
				123I-mIBG (Contrast enhanced CT (cCT) or Cardiac MRI (CMR))	觸糧鏇積襯蓋獵選衊鏇(築鹹簾鑰齋鬱範蓋餘簾) = 壓鬱夢願範顧艱夢襯鏇糧遞網繭糧鑰憲艱餘醖 (壓膚選鬱積築築襯襯網 )