18F-Fluoromisonidazole(18F-Fluoromisonidazole) - 在研适应症：肝细胞癌，高级别胶质瘤，缺氧_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

FMISO

+ [1]

靶点-

作用方式-

作用机制-

治疗领域

肿瘤消化系统疾病神经系统疾病+ [1]

在研适应症

肝细胞癌高级别胶质瘤缺氧

非在研适应症-

原研机构

Advanced Imaging Projects LLC

在研机构

Weill Medical College of Cornell UniversityAdvanced Imaging Projects LLC

The University of Texas at Austin

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C6H8FN3O3

InChIKeyHIIJZYSUEJYLMX-JZRMKITLSA-N

CAS号104613-87-8

关联

36

项与 18F-Fluoromisonidazole 相关的临床试验

NCT04332588

/ Recruiting临床1期IIT

Monitoring HER2+ Breast Cancer Neoadjuvant Treatment With Advanced PET/MRI

The purpose of the study is to see if using an investigational drug called [18F]FMISO with PET/MRI imaging can help monitor and predict the effect of trastuzumab (Herceptin) on chemotherapy in patients diagnosed with advanced HER2 positive breast cancer. This study is for imaging purposes only and is not a treatment study. The results of this study will not change a patient's clinical treatment plan but it may help physicians and researchers better understand how best to treat patients with breast cancer in the future.

开始日期2025-04-01

申办/合作机构

The University of Alabama at Birmingham

NCT05996432

/ Recruiting早期临床1期IIT

Non-invasive, Image-Based, In-Vivo Assessment of Tumor Hypoxia to Guide Hypoxia-Driven Adaptive Radiation Therapy

This study will apply novel MRI approaches with established sensitivity to tissue oxygen consumption and perfusion to predict hypoxia-associated radiation resistance, manifested as tumor recurrence and progression post-treatment.

开始日期2023-05-17

申办/合作机构

The Vanderbilt-Ingram Cancer Center

[+1]

NCT04846309

/ Recruiting临床1期IIT

Hypoxia Imaging for Esophageal Cancer to Guide Personalized Radiation Therapy

This is a Phase I trial evaluating the safety of personalized radiation therapy based on levels of hypoxia identified on FMISO-PET and MRI. All patients will receive a baseline FMISO positron emission tomography (PET) and MRI to identify levels of hypoxia. Patients with tumor hypoxia will receive a higher dose of radiation therapy. Subjects who do not have hypoxic tumors will be treated with the standard-of-care radiation regimen. After fraction 10 of radiation therapy, an additional MRI will be performed. If this interim MRI demonstrates little or no response (as defined in Section 6), an optional boost radiation dose can be administered.
Trial enrollment will be conducted in two parts. In Part 1, eight patients will be enrolled. After all eight patients have completed the 30 day dose-limiting toxicity (DLT) period, enrollment will be placed on hold and safety will be evaluated. During the interim analysis, one additional patient will be allowed to be enrolled in the trial. If the trial meets stopping rules as described in Section 11.3, the trial will be re-evaluated by the Data and Safety Monitoring Committee (DSMC) and the Principal Investigator. However, if the rate of DLTs remains below the unacceptable toxicity rate, enrollment will open to the enrollment of eight more patients.

开始日期2021-10-12

申办/合作机构

University of Utah

100 项与 18F-Fluoromisonidazole 相关的临床结果

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100 项与 18F-Fluoromisonidazole 相关的转化医学

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100 项与 18F-Fluoromisonidazole 相关的专利（医药）

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361

项与 18F-Fluoromisonidazole 相关的文献（医药）

2024-11-01·Journal of Radioanalytical and Nuclear Chemistry

Evaluation of an automated synthesis method for [18F]Fluoromisonidazole using a Scintomics GRP® module

作者: Rubow, Sietske ; Oliver, Jayed ; Le Roux, Jannie

AbstractThere is limited information on utilizing commercially supplied [18F]Fluoride from an off-site cyclotron for the synthesis of radiopharmaceuticals. This study explored the production of the PET hypoxia marker [18F]FMISO, using the Scintomics® GRP module and distantly produced [18F]Fluoride, which lacks published data. A radiochemical yield of 27.4 ± 3.6% (n = 5) and high radiochemical purity were achieved in synthesis time of 48 min. The [18F]FMISO met all Ph. Eur. standards, demonstrating the consistency and reliability of the module in generating a clinical-grade radiopharmaceutical using off-site produced [18F]Fluoride, but available patient doses were severely limited.

2024-11-01·Biomedical Physics & Engineering Express

Mathematical modeling of ¹⁸F-Fluoromisonidazole (¹⁸F-FMISO) radiopharmaceutical transport in vascularized solid tumors

Article

作者: Rahmim, Arman ; Abazari, Mohammad Amin ; Eydi, Faezeh ; Kashkooli, Farshad Moradi ; Soltani, M

Abstract18F-Fluoromisonidazole (18F-FMISO) is a highly promising positron emission tomography radiopharmaceutical for identifying hypoxic regions in solid tumors. This research employs spatiotemporal multi-scale mathematical modeling to explore how different levels of angiogenesis influence the transport of radiopharmaceuticals within tumors. In this study, two tumor geometries with heterogeneous and uniform distributions of capillary networks were employed to incorporate varying degrees of microvascular density. The synthetic image of the heterogeneous and vascularized tumor was generated by simulating the angiogenesis process. The proposed multi-scale spatiotemporal model accounts for intricate physiological and biochemical factors within the tumor microenvironment, such as the transvascular transport of the radiopharmaceutical agent, its movement into the interstitial space by diffusion and convection mechanisms, and ultimately its uptake by tumor cells. Results showed that both quantitative and semi-quantitative metrics of 18F-FMISO uptake differ spatially and temporally at different stages during tumor growth. The presence of a high microvascular density in uniformly vascularized tumor increases cellular uptake, as it allows for more efficient release and rapid distribution of radiopharmaceutical molecules. This results in enhanced uptake compared to the heterogeneous vascularized tumor. In both heterogeneous and uniform distribution of microvessels in tumors, the diffusion transport mechanism has a more pronounced than convection. The findings of this study shed light on the transport phenomena behind 18F-FMISO radiopharmaceutical distribution and its delivery in the tumor microenvironment, aiding oncologists in their routine decision-making processes.

2024-10-01·Journal of Nuclear Medicine

Development of¹⁸F-Fluoromisonidazole Hypoxia PET/CT Diagnostic Interpretation Criteria and Validation of Interreader Reliability, Reproducibility, and Performance

Article

作者: Michaud, Laure ; Schöder, Heiko ; Wray, Rick ; Yeh, Randy ; Humm, John ; Leithner, Doris ; Wong, Richard ; Riaz, Nadeem ; Mirtcheva, Rosna ; Mauguen, Audrey ; Sherman, Eric ; Lee, Nancy

Tumor hypoxia, an integral biomarker to guide radiotherapy, can be imaged with ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) hypoxia PET. One major obstacle to its broader application is the lack of standardized interpretation criteria. We sought to develop and validate practical interpretation criteria and a dedicated training protocol for nuclear medicine physicians to interpret ¹⁸F-FMISO hypoxia PET. Methods: We randomly selected 123 patients with human papillomavirus-positive oropharyngeal cancer enrolled in a phase II trial who underwent 123 ¹⁸F-FDG PET/CT and 134 ¹⁸F-FMISO PET/CT scans. Four independent nuclear medicine physicians with no ¹⁸F-FMISO experience read the scans. Interpretation by a fifth nuclear medicine physician with over 2 decades of ¹⁸F-FMISO experience was the reference standard. Performance was evaluated after initial instruction and subsequent dedicated training. Scans were considered positive for hypoxia by visual assessment if ¹⁸F-FMISO uptake was greater than floor-of-mouth uptake. Additionally, SUV_max was determined to evaluate whether quantitative assessment using tumor-to-background ratios could be helpful to define hypoxia positivity. Results: Visual assessment produced a mean sensitivity and specificity of 77.3% and 80.9%, with fair interreader agreement (κ = 0.34), after initial instruction. After dedicated training, mean sensitivity and specificity improved to 97.6% and 86.9%, with almost perfect agreement (κ = 0.86). Quantitative assessment with an estimated best SUV_max ratio threshold of more than 1.2 to define hypoxia positivity produced a mean sensitivity and specificity of 56.8% and 95.9%, respectively, with substantial interreader agreement (κ = 0.66), after initial instruction. After dedicated training, mean sensitivity improved to 89.6% whereas mean specificity remained high at 95.3%, with near-perfect interreader agreement (κ = 0.86). Conclusion: Nuclear medicine physicians without ¹⁸F-FMISO hypoxia PET reading experience demonstrate much improved interreader agreement with dedicated training using specific interpretation criteria.

1

项与 18F-Fluoromisonidazole 相关的新闻（医药）

2024-12-27

·小核说核药

肿瘤诊疗一体化核药的创新研究——融合“精准靶向+乏氧滞留”双重机制！

今天因为你的分享，让小核元气满满！ FOCUS ON Xiaohe 点击蓝字.催更小核小核微信| xiaoheshuoheyao777 聚焦领域| 放射性药物与临床核医学 2024年12月22日，美国宾夕法尼亚大学医学院放射学系孔繁渊（Hank F. Kung）和北京师范大学化学学院教授朱霖教授为共同通讯在《Journal of Medicinal Chemistry》期刊正式发表了题为“Development of [68Ga]Ga/[177Lu]Lu-DOTA-NI-FAPI-04 Containing a Nitroimidazole Moiety as New FAPI Radiotracers with Improved Tumor Uptake and Retention”的研究论文，报道了含硝基咪唑基团的新FAPI放射性示踪剂的开发！可下载原文拜读：DOI: 10.1021/acs.jmedchem.4c02015 相关往期链接：一切过往皆为序章：[177Lu]Lu-P15-073的首个临床研究结果揭晓 PSMA新核药[18F]AlF-P16-093首次人体研究！ [68Ga]Ga-P16-093 和 [68Ga]Ga-PSMA-11的头对头比较硬核来袭！新FAP核药：68Ga-HBED-CC-FAPI！ 68Ga-P16-093和18-FDG 在肾透明细胞癌患者中的头对头比较 01. 研究简介本文阐述了一种创新性FAP靶向放射性药物（[68Ga/177Lu]Ga/Lu-1），该药物采用“精准靶向+乏氧保留”双重机制，旨在实现肿瘤的精准诊断与高效治疗： 1.对FAP具有高亲和力：新型放射性药物[68Ga/177Lu]Ga/Lu-1对FAP表现出显著的亲和力（IC50 = 7.44 nM），其肿瘤细胞摄取量远超不含硝基咪唑乏氧基团的对照物[68Ga/177Lu]Ga/Lu-FAPI-04。这种增强的亲和力有望提升其肿瘤靶向治疗的效果。 2.优异的PET成像与生物分布：U87MG肿瘤小鼠的PET成像与生物分布研究显示，[68Ga/177Lu]Ga/Lu-1在肿瘤摄取、保留时间以及肿瘤与背景比值方面均优于对照组。这些结果提示[68Ga/177Lu]Ga/Lu-1具有更佳的肿瘤特异性成像和治疗潜力。 3.硝基咪唑（NI）基团的重要性：体外与体内实验均证实了硝基咪唑（NI）基团在增强药物有效性方面的关键作用。该基团有助于药物在肿瘤细胞内的积累和保留，从而延长靶向治疗的持续时间并提升其疗效。 4.初步临床前结果与进行中的临床研究：初步临床前数据表明[68Ga/177Lu]Ga/Lu-1是具有前景的FAP靶向诊断与治疗候选药物。目前，临床试验正在进行中，旨在进一步验证其临床应用潜力。 [68Ga/177Lu]Ga/Lu-1作为一种新型FAP靶向放射性药物，展现出卓越的肿瘤靶向性和保留特性，其部分原因在于加入了硝基咪唑基团。这些早期的临床前发现突显了其在癌症综合诊断与治疗领域的应用前景，目前相关临床研究正在深入探索其潜力。这一“精准靶向+乏氧滞留”双机制创新思路为肿瘤诊疗一体化核药的创新研究开辟了新的方向。 02. 亮点解析 1. 前体合成及放射性标记：基于FAPI-04结构，成功引入2-硝基咪唑结构（NI）得到DOTA-NI-FAPI-04（化合物1），并顺利完成Ga-68和Lu-177标记。 2.体外细胞实验结果： 1.化合物1对FAP表现出低钠摩尔的结合亲和力（IC50: 7.44 ± 1.11 nM）； 2.在常氧条件下，[68Ga]Ga-1和[177Lu]Lu-1的肿瘤细胞摄取量在所有观测时间点均显著高于相应的[68Ga]Ga-FAPI-04和[177Lu]Lu-FAPI-04； 3.细胞流出实验表明：[177Lu]Lu-1在乏氧条件下的细胞滞留效果优于常氧条件，而[177Lu]Lu-FAPI-04在常氧和乏氧条件下的细胞流出没有显著性差异； 4.结论：硝基咪唑的引入显著增加了药物在乏氧条件下的细胞摄取。 3.荷瘤鼠体内PET显像及生物分布结果： 1.在荷U87MG肿瘤小鼠研究显示：[68Ga/177Lu]Ga/Lu-1的肿瘤摄取和滞留显著优于[68Ga/177Lu]Ga/Lu-FAPI-04，且肿瘤背景比更高； 2.荷HT1080-FAP肿瘤鼠PET显像结果显示：肿瘤乏氧程度越高（即[18F]FMISO摄取越高），[68Ga]Ga-1的肿瘤摄取也越高，且与[68Ga]Ga-FAPI-04的肿瘤摄取差异越大，表明硝基咪唑基团显著提高了药物在肿瘤乏氧区域的摄取和滞留。研究总结 [68Ga/177Lu]Ga/Lu-1对FAP具有高亲和力，肿瘤细胞摄取量数倍高于不含硝基咪唑基团的对照物[68Ga/177Lu]Ga/Lu-FAPI-04；在荷U87MG肿瘤小鼠中，[68Ga/177Lu]Ga/Lu-1的肿瘤摄取量、滞留时间和肿瘤/背景比值均显著优于对照组；体内外实验均验证了硝基咪唑（NI）基团的关键作用；研究结果显示[68Ga/177Lu]Ga/Lu-1是一种潜力巨大的新型肿瘤靶向诊疗一体化核药，临床研究正在进行中。未来展望[68Ga/177Lu]Ga/Lu-1作为一种新型 FAP 靶向放射性药物，展现出巨大的潜力，其出色的肿瘤靶向性和保留特性得益于硝基咪唑基团的加入。预示了其在癌症综合诊断与治疗领域的广阔应用前景。这一“精准靶向+乏氧滞留”双机制创新思路为肿瘤诊疗一体化核药的创新研究开辟了新的方向[1,2]。 REFERENCES： 1. Luo, Yang, et al. "Development of [68Ga/177Lu]Ga/Lu-DOTA-NI-FAPI-04 Containing a Nitroimidazole Moiety as New FAPI Radiotracers with Improved Tumor Uptake and Retention."Journal of Medicinal Chemistry (2024). 2. Luo, Yang, et al. "68Ga/177Lu-Labeled Bivalent Agents for Targeting Hypoxia and PSMA-Binding in Prostate Cancer."Journal of Medicinal Chemistry 67.15 (2024): 13491-13506. 课题组介绍朱霖教授课题组长城秋游合照（右起第五位：朱霖教授；第六位：孔繁渊教授）北京师范大学朱霖教授课题组与美国孔繁渊（Hank F Kung）教授合作，长期致力于放射性药物的研发及临床转化，始终走在放射性药物研究的前沿。研究领域涵盖多种放射性药物发现与开发，包括F-18标记的探针，如AD探针（[18F]-AV45、[18F]-AV1和[18F]-D3FSP）、VMAT2靶向探针（[18F]FP-(+)-DTBZ 和D6-[18F]FP-(+)-DTBZ）、SRET靶向探针（[18F]FPBM & [18F]FPBM 2）以及 [18F]-Glutamine（肿瘤谷氨酰胺代谢）等；Ga-68和Lu-177标记的PSMA靶向药物，如[68Ga]Ga-P16-093、[68Ga/177Lu]Ga/Lu-P17-087、[68Ga/177Lu]Ga/Lu-P17-088、[68Ga/177Lu]Ga/Lu-AAZTA-NI-PSMA-093等；Ga-68和Lu-177标记的双磷酸盐药物，如[68Ga]Ga-P15-041、[68Ga/177Lu]Ga/Lu-P15-073等；Ga-68和Lu-177标记的FAP靶向药物，如[68Ga]Ga-HBED-CC-FAPI、[68Ga]Ga-DOTA-NI-FAPI-04等；以及Ga-68标记的GLP-1R靶向药物（[68Ga]Ga-HBED-CC-exendin-4等）。课题组在放射性药物设计、合成、放射性标记、生物评价及临床转化方面取得显著成果，培养了优秀专业人才，许多毕业生已在高校、医院等机构从事科研和临床工作。 ●新CLDN18.2靶向核药重磅来袭！ ●68Ga-FAP-2286精准诊断尿路上皮癌！ ●新TROP2靶向核药重磅来袭！声明：本文观点仅代表小核本人，视角局限，欢迎批评指正；如需转载，请务必注明文章作者和来源。如有其它问题，请在本平台留言或联系xiaoheshuoheyao777@163.com，小核将在第一时间处理。内容 | 朱霖教授课题组图文排版 | 小核媒体合作 | 科研宣传 | 转载开白 xiaoheshuoheyao777（小核微信）

放射疗法临床结果

100 项与 18F-Fluoromisonidazole 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	18F-Fluoromisonidazole	-	DB14830

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
肝细胞癌	临床2期	-	The University of Texas at Austin	-
肝细胞癌	临床2期	-	Advanced Imaging Projects LLC	-
高级别胶质瘤	临床1期	美国	Weill Medical College of Cornell University	2021-02-01
缺氧	临床1期	美国	Weill Medical College of Cornell University	2021-02-01

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临床结果

适应症

分期

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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


ASTRO2024	N/A	头颈部鳞状细胞癌	-	18F-Fluoromisonidazole (FMISO PET positive for tumor hypoxia)	(衊廠構鹹鑰鏇選獵獵壓) = 製廠壓艱鬱網鹽膚鹹選餘齋繭夢鹽齋鑰鹹壓壓 (鏇憲選觸憲築構簾簾範 ) 更多	-	2024-10-01
ASTRO2024	N/A	头颈部鳞状细胞癌	-	18F-Fluoromisonidazole (FMISO PET negative for tumor hypoxia)	-	-	2024-10-01
NCT03303469 (CTgov)	临床2期	肝细胞癌	3	FMISO	遞範鑰獵糧製糧願窪憲(鹽範糧簾衊顧築鹹憲繭) = 艱鏇獵醖製夢醖窪餘鹹顧獵網醖選簾憲醖獵網 (簾積糧壓齋憲憲醖鑰網, 獵製製齋淵窪鬱鹹鹽願 ~ 夢窪艱廠餘壓醖獵製壓) 更多	-	2021-02-21
EANM2019	N/A	肺癌 CD34 \| GLUT-1 \| CAIX ... 更多	20	[18F]-FMISO	鬱選網範膚夢淵餘齋蓋(壓範窪獵鹹鬱夢鏇憲鑰) = 蓋糧廠糧觸範醖窪糧醖糧築糧壓衊艱構衊鏇獵 (遞遞齋構顧築淵壓選製, 25.8)	积极	2019-09-18
EANM2019	N/A	肺癌 CD34 \| GLUT-1 \| CAIX ... 更多	20	[18F]-FMISO ([18F]-FAZA)	鬱選網範膚夢淵餘齋蓋(壓範窪獵鹹鬱夢鏇憲鑰) = 顧築艱糧餘憲糧醖窪醖糧築糧壓衊艱構衊鏇獵 (遞遞齋構顧築淵壓選製, 13.76)	积极	2019-09-18
SNMMI2019	N/A	心脏结节病	-	FMISOFDGSO (FDG PET)	餘醖膚鑰鹹鏇鹽壓壓憲(衊觸構衊鏇築餘積繭積) = 衊醖鑰鏇願蓋簾遞築構選獵願淵築顧壓衊網鹽 (鬱醖糧膚積襯醖醖蓋淵, 1.71)	-	2019-05-21
NCT02471313 (CTgov)	临床2期	肝细胞癌	3	[18F] FMISO	窪窪壓醖窪構製鑰積蓋(獵蓋醖製鏇築製醖遞蓋) = 構簾網遞鑰淵淵餘醖餘範獵選鹽製簾鹹築膚窪 (齋觸艱憲蓋壓顧築選廠, 觸獵壓網鏇淵齋餘選夢 ~ 遞願網壓窪製齋壓選廠) 更多	-	2019-04-23
ASTRO2015	N/A	非小细胞肺癌Ⅰ期	-	18F-fluoromisonidazole (FMISO-PET/CT before SBRT)	艱膚觸窪壓顧願蓋糧膚(壓夢簾艱蓋壓顧鏇鬱遞) = 鏇膚憲鑰糧壓繭遞構構憲鑰醖遞糧鹹淵顧鹹淵 (襯鑰鏇鑰鏇觸遞窪蓋選 )	-	2015-11-01
ASTRO2015	N/A	非小细胞肺癌Ⅰ期	-	18F-fluoromisonidazole (FMISO-PET/CT after SBRT)	艱膚觸窪壓顧願蓋糧膚(壓夢簾艱蓋壓顧鏇鬱遞) = 範網簾窪蓋鏇鹽築鑰襯憲鑰醖遞糧鹹淵顧鹹淵 (襯鑰鏇鑰鏇觸遞窪蓋選 )	-	2015-11-01
SNMMI2015	N/A	非小细胞肺癌	-	18 FMISO (NSCLC patients)	鑰壓製廠窪築築積製廠(鹽構夢獵鬱窪憲觸鹽齋) = 鑰齋窪顧構艱觸願範壓齋齋壓構築艱築鏇齋憲 (鹽衊選壓遞鏇憲簾積製, 0.092 ~ 0.33) 更多	-	2015-05-15
SNMMI2015	N/A	非小细胞肺癌	-	18F-FMISOO (18F-FMISO PET/CT scan)	醖鏇遞餘顧餘憲鏇構壓(淵積膚網餘鏇餘範觸鏇) = 鹽築選積醖餘築鏇淵衊構壓齋築顧鹹艱遞壓製 (餘壓艱鹽觸鬱憲襯製窪, 1.0)	-	2015-05-15
ASTRO2014	N/A	脊索瘤	-	18F-FMISO (Proton or combined proton/photon RT)	簾簾獵廠淵遞積艱鏇顧(簾艱膚鬱構鏇醖鏇觸衊) = 觸夢醖積餘壓築醖構遞網遞壓鹽鏇鏇蓋夢衊積 (艱齋襯齋鑰窪觸醖顧簾 )	-	2014-09-01
ASTRO2012	N/A	胶质母细胞瘤	-	[18F]-Fluoromisonidazole-Positron Emission Tomography	憲齋鏇壓鹽夢壓積憲襯(鏇齋壓繭鏇壓艱壓製簾) = 網壓範範衊醖廠醖膚窪鑰築觸醖淵網鹽網觸膚 (淵網網鑰憲鏇製衊製膚, 10.7) 更多	-	2012-11-01
ASTRO2012	N/A	胶质母细胞瘤	-	[18F]-Fluoromisonidazole (MRI)	憲齋鏇壓鹽夢壓積憲襯(鏇齋壓繭鏇壓艱壓製簾) = 蓋製鏇糧鹹積鬱構醖夢鑰築觸醖淵網鹽網觸膚 (淵網網鑰憲鏇製衊製膚, 26.6) 更多	-	2012-11-01