This is an open label study to compare three new generation TAU radioligands, 18F-RO948 (formerly known as 18F-6958948), 18F-MK6240, and [18F]GTP1for imaging of taupathy and demonstrate their absence of off-target binding in patients with Alzheimer disease (AD) and older healthy controls (OC). The study will directly compare AD and OC with these three next-generation TAU radioligands and compare each of them with historical data of the current most widely used first generation radioligand, 18F-AV1451. Upto38 (30 AD (Amyloid +)and 8 OC (Amyloid -), matched for age and sex with A+ subjects) male and female subjects aged 50-100 will be enrolled in this study protocol: up to 8 for Cohort 1, up to 8 for Cohort 2, and up to 22 for Cohort 3. The study consists of three cohorts: Cohort 1: Up to8 AD subjects (A+; CDR 0.5 and 1)will receive two PET scans in random order, with receiving either18F-RO948 or18F-MK6240 at the first scan. A third scan with 18F-GTP1is possible, depending on timing and radiotracer availability Cohort 2:Up to8 OC (A-; CDR=0)subjects will receive two PET scans in random order, with receiving either18F-RO948or 18F-MK6240 at the first scan. A third scan with 18F-GTP1is possible, depending on timing and radiotracer availability Cohort 3:Up to 22 (A+; CDR = 0, .5 and 1) subjects will receive three PET scans in random order, with receiving 18F-RO94818F-MK6240 or18F-GTP1at the first scan. Efforts will be made to include about 1/3 CDR = 0, 1/3 CDR .5, and 1/3 CDR 1 in Cohort 3.

开始日期2023-02-01

申办/合作机构

Washington University School of Medicine

[+1]

NCT04437290 / Not yet recruitingN/AIIT

University of Washington Alzheimer's Disease Research Center (UW ADRC) Imaging & Biomarker Core

This is a cross-sectional, observational study that characterizes research participants with Alzheimer's disease (AD) for their patterns of brain degeneration with the investigational tau positron emission tomography (PET) radiotracer [18F] MK-6240. The goal is to describe the topographic pattern of involvement of cerebral brain regions (topographic phenotyping) in early stage AD participants using tau PET in a sub-cohort of the University of Washington Alzheimer's Disease Research Center (ADRC) Clinical Cohort, and to make this phenotype information available to affiliated research studies at the University of Washington and to the general scientific community via the National Alzheimer's Coordinating Center.

开始日期2022-11-01

申办/合作机构

University of Washington

[+2]

100 项与 Florquinitau F18 相关的临床结果

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100 项与 Florquinitau F18 相关的转化医学

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100 项与 Florquinitau F18 相关的专利（医药）

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项与 Florquinitau F18 相关的文献（医药）

2024-06-01·Acta Neuropathologica

Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases

Article

作者: Amaral, Ana C ; Johnson, Keith ; Moon, S-H ; Scapellato, Margaret ; Frosch, Matthew P ; Gómez-Isla, Teresa ; Neelamegam, Ramesh ; Dhaynaut, Maeva ; El Fakhri, Georges ; Kumar, Sunny ; Normandin, Marc D ; Aguero, Cinthya ; Carazo-Casas, Carlos

AbstractWe and others have shown that [18F]-Flortaucipir, the most validated tau PET tracer thus far, binds with strong affinity to tau aggregates in Alzheimer's (AD) but has relatively low affinity for tau aggregates in non-AD tauopathies and exhibits off-target binding to neuromelanin- and melanin-containing cells, and to hemorrhages. Several second-generation tau tracers have been subsequently developed. [18F]-MK-6240 and [18F]-PI-2620 are the two that have garnered most attention. Our recent data indicated that the binding pattern of [18F]-MK-6240 closely parallels that of [18F]-Flortaucipir. The present study aimed at the direct comparison of the autoradiographic binding properties and off-target profile of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 in human tissue specimens, and their potential binding to monoamine oxidases (MAO). Phosphor-screen and high resolution autoradiographic patterns of the three tracers were studied in the same postmortem tissue material from AD and non-AD tauopathies, cerebral amyloid angiopathy, synucleopathies, transactive response DNA-binding protein 43 (TDP-43)-frontotemporal lobe degeneration and controls. Our results show that the three tracers show nearly identical autoradiographic binding profiles. They all strongly bind to neurofibrillary tangles in AD but do not seem to bind to a significant extent to tau aggregates in non-AD tauopathies pointing to their limited utility for the in vivo detection of non-AD tau lesions. None of them binds to lesions containing β-amyloid, α-synuclein or TDP-43 but they all show strong off-target binding to neuromelanin and melanin-containing cells, as well as weaker binding to areas of hemorrhage. The autoradiographic binding signals of the three tracers are only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline suggesting that MAO enzymes do not appear to be a significant binding target of any of them. These findings provide relevant insights for the correct interpretation of the in vivo behavior of these three tau PET tracers.

2024-05-01·European Journal of Nuclear Medicine and Molecular Imaging

The spatial extent of tauopathy on [18F]MK-6240 tau PET shows stronger association with cognitive performances than the standard uptake value ratio in Alzheimer’s disease

Article

作者: Hanseeuw, Bernard ; Huyghe, Lara ; Dricot, Laurence ; Quenon, Lisa ; Gérard, Thomas ; Malotaux, Vincent ; Colmant, Lise ; Lhommel, Renaud ; Salman, Yasmine ; Ivanoiu, Adrian

AbstractPurpose[18F]MK-6240, a second-generation tau PET tracer, is increasingly used for the detection and the quantification of in vivo cerebral tauopathy in Alzheimer’s disease (AD). Given that neurological symptoms are better explained by the topography rather than by the nature of brain lesions, our study aimed to evaluate whether cognitive impairment would be more closely associated with the spatial extent than with the intensity of tau-PET signal, as measured by the standard uptake value ratio (SUVr).Methods[18F]MK6240 tau-PET data from 82 participants in the AD spectrum were quantified in three different brain regions (Braak ≤ 2, Braak ≤ 4, and Braak ≤ 6) using SUVr and the extent of tauopathy (EOT, percentage of voxels with SUVr ≥ 1.3). PET data were first compared between diagnostic categories, and ROC curves were computed to evaluate sensitivity and specificity. PET data were then correlated to cognitive performances and cerebrospinal fluid (CSF) tau values.ResultsThe EOT in the Braak ≤ 2 region provided the highest diagnostic accuracies, distinguishing between amyloid-negative and positive clinically unimpaired individuals (threshold = 9%, sensitivity = 79%, specificity = 82%) as well as between prodromal AD and preclinical AD (threshold = 38%, sensitivity = 81%, specificity = 93%). The EOT better correlated with cognition than SUVr (∆R2 + 0.08–0.09) with the best correlation observed for EOT in the Braak ≤ 4 region (R2 = 0.64). Cognitive performances were more closely associated with PET metrics than with CSF values.ConclusionsQuantifying [18F]MK-6240 tau PET in terms of EOT rather than SUVr significantly increases the correlation with cognitive performances. Quantification in the mesiotemporal lobe is the most useful to diagnose preclinical AD or prodromal AD.

2024-01-22·Journal of Chemical Information and Modeling

Docking for Molecules That Bind in a Symmetric Stack with SymDOCK

Article

作者: Kormos, Rian C. ; Pepe, Joseph G. ; DeGrado, William F. ; Smith, Matthew S. ; Irwin, John J. ; Shoichet, Brian K. ; Diamond, Marc I. ; Shahmoradian, Sarah H. ; Knight, Ian S. ; Kunach, Peter

Discovering ligands for amyloid fibrils, such as those formed by the tau protein, is an area of great current interest. In recent structures, ligands bind in stacks in the tau fibrils to reflect the rotational and translational symmetry of the fibril itself; in these structures, the ligands make few interactions with the protein but interact extensively with each other. To exploit this symmetry and stacking, we developed SymDOCK, a method to dock molecules that follow the protein's symmetry. For each prospective ligand pose, we apply the symmetry operation of the fibril to generate a self-interacting and fibril-interacting stack, checking that doing so will not cause a clash between the original molecule and its image. Absent a clash, we retain that pose and add the ligand-ligand van der Waals energy to the ligand's docking score (here using DOCK3.8). We can check these geometries and energies using an implementation of ANI, a neural-network-based quantum-mechanical evaluation of the ligand stacking energies. In retrospective calculations, symmetry docking can reproduce the poses of three tau PET tracers whose structures have been determined. More convincingly, in a prospective study, SymDOCK predicted the structure of the PET tracer MK-6240 bound in a symmetrical stack to AD PHF tau before that structure was determined; the docked pose was used to determine how MK-6240 fit the cryo-EM density. In proof-of-concept studies, SymDOCK enriched known ligands over property-matched decoys in retrospective screens without sacrificing docking speed and can address large library screens that seek new symmetrical stackers. Future applications of this approach will be considered.

项与 Florquinitau F18 相关的新闻（医药）

2024-09-09

·Business Wire

Enigma Biomedical - USA Announces Collaboration with Alamar Biosciences to Advance the Field of Diagnostics for Neurodegenerative Diseases

KNOXVILLE, Tenn. & FREMONT, Calif.--( BUSINESS WIRE )--Enigma Biomedical USA (EB) today announced a collaboration with Alamar Biosciences in the field of neurology. Through this collaboration, EB has a non-exclusive right to introduce Alamar’s protein detection and measurement technologies, including its ARGO™ HT instrument and NULISA™ reagent kits, to academic and pharma customers in the field of neurology research. “We are excited to collaborate with Enigma to combine the power of high sensitivity, multiplexed immunoassays with high quality imaging to advance the field of neuro diagnostics,” said Yuling Luo, Founder, Chairman and CEO of Alamar Biosciences. This collaboration is designed to yield a large data set of results from neuroimaging and immunoassay from biofluids, which, together, are expected to lead to the development of more efficient diagnostic workflow solutions for patient-centric therapies. Through its affiliate, Enigma Biointelligence (EBI), EB will enable users to order Alamar’s high sensitivity, high specificity immunoassays directly from EBI’s Minerva Bio Platform software. EBI’s Health Grid software will then allow academic and pharma study sponsors to collect, manage and interpret data generated within their studies, including data generated using EB’s PET tracers and the NULISA biofluid based tests. Through this collaboration, EB and Alamar expect to develop analytics products using data generated by shared customers. “Enigma and our affiliate companies are focused on providing information and technologies to researchers and clinicians to improve brain health,” said Rick Hiatt, Chief Executive Officer of Enigma Biomedical USA. “We are thrilled to welcome Alamar to our growing list of first-class partners, who all together share our company’s mission and vision.” “I am confident that the combination of Alamar’s and EBI’s technologies will deliver scalable and accessible diagnostic solutions for patients,” said Dr. Hartmuth Kolb, Chief Scientific Officer of Enigma Biomedical USA. About Enigma Biomedical - USA Enigma Biomedical USA’s vision is to be the premier provider of imaging biomarkers for neurological pathologies, associated information technology, and related tools to accelerate the development, approval, and adoption of effective therapies to treat neurodegenerative diseases. EB’s neuroimaging biomarkers provide Pharma and Academic researchers with state of the art tools for enabling Disease-Modifying Therapy development with the highest precision and accuracy. In pursuit of this vision, subsidiaries of EB have provided the best-in-class Tau and Amyloid PET imaging biomarkers, MK-6240 and NAV-4694, to our partners to enable their research efforts. Both tracers have recently been acquired by a third party for further development. EB also recently announced a partnership with AbbVie to explore their novel 4R Tau PET Imaging Biomarkers.

2024-07-23

·先通医药

先通医药海外参股公司Meilleur及其Aβ-PET显像剂NAV-4694被收购

近日,先通医药海外参股公司Meilleur及其用于治疗阿尔茨海默病的新一代Aβ-PET显像剂NAV-4694被纳斯达克上市公司Lantheus收购。美国国家老龄化研究所和阿尔茨海默病协会（NIA-AA）工作组最新发布的修订版指南指出，阿尔茨海默病应使用基于蛋白质的生物标志物进行生物学定义，包括Aβ和Tau在内的生物标志物可用于诊断阿尔茨海默病并提供其严重程度的指标。1 NAV-4694目前正处于临床Ⅲ期开发阶段，已被广泛用于学术和行业的研究性治疗试验。NAV-4694与Lantheus的下一代18F 标记Tau-PET显像剂MK-6240（florquinitau）形成互补，扩大了Lantheus的阿尔茨海默病诊断产品组合。 MK-6240是一款18F标记的高亲和力Tau蛋白PET显像剂。该药物对Tau蛋白的探测显像对比度高，可无创、精准、定位、定量地呈现阿尔兹海默病患者脑部Tau蛋白沉积的病理变化。此前，Lantheus通过收购Cerveau公司获得了MK-6240的全球权益，而先通医药是Cerveau的股东之一。根据现有的再许可协议，先通医药保留了MK-6240在中国的权益。 Aβ-PET阳性显像能够提示存在AD病理改变，结合Tau-PET检测结果，对AD早期诊断、鉴别诊断、抗Aβ治疗后疗效评价、AD药物临床试验患者筛选具有显著价值。根据协议条款，Lantheus 将支付预付款及潜在的额外开发和商业里程碑付款。此外，Lantheus 还将为研究收入和商业销售支付特许权使用费。该协议以股票购买的形式签订，规定Meilleur将在交易完成后的规定时间内提供过渡和临床开发服务。先通医药CEO唐艳旻表示：“这是一次激动人心的收购，我们非常看好Aβ-PET和Tau-PE在阿尔茨海默病早期诊断，临床分期及治疗前后疗效评估等方面的应用潜力,它们的联合使用将为阿尔茨海默病的诊疗决策提供有力的证据。” 在中国,先通医药则通过Aβ-PET显像剂欧韦宁®氟[18F]贝他苯注射液与Tau-PET显像剂MK-6240的组合,助力阿尔茨海默病患者实现早诊早治。参考文献 1.Jack CR, et.al. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimer’s Dement 2024;1-27. https://doi.org/10.1002/alz.13859 先通医药是中国创新放射性药物领域的领先企业，专注于放射性药物的研发创新及落地应用以改善患者的健康水平。先通医药于2014年正式开展新一代放射性药物的研发，总部位于北京，在上海设有研发中心，在江苏、广东、四川建设有现代化放射性药物智能生产基地；同时，在美国设有分支机构，并与十几家跨国药企达成战略合作。全球放射性药物主要应用于神经、心血管、肿瘤三大疾病领域，先通医药已实现全面布局，并拥有20+精准诊断和靶向治疗放射性药物研发管线。凭借自身的研发优势，先通医药获得了投资机构的青睐，2020年4月至今，已成功募资超20亿元人民币，未来不久将登陆主要资本市场，成为中国放射性药物领域的创新力量。内容来源于网络，如有侵权，请联系删除。

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2024-07-15

·FierceBiotech

Lantheus acquires Alzheimer’s PET diagnostic developer Meilleur Technologies

Lantheus pitched Meilleur’s amyloid-targeting NAV-4694 as a complement to its PET agent MK-6240, which is aimed at Alzheimer’s tau tangles. Lantheus is expanding its holdings of PET imaging agents for Alzheimer’s disease, with the acquisition of Meilleur Technologies. The deal grants Lantheus exclusive worldwide rights to Meilleur’s radiopharmaceutical diagnostic that highlights beta amyloid plaques in the brain. The injectable agent—known as NAV-4694, or F18-flutafuranol—is currently in phase 3 development. The acquisition comes just days after the Centers for Medicare and Medicaid Services proposed a separate payment pathway for certain diagnostic radiopharmaceuticals and nuclear medicine imaging agents—instead of bundling them as part of the procedure, as it had in the past. The change was put forward in CMS’ proposal for payment systems among hospital outpatient services and ambulatory surgical centers, set for the 2025 calendar year. Lantheus’ stock price jumped nearly 60% on the news. The deal also follows the FDA’s approval earlier this month of Eli Lilly’s Kisunla (donanemab-abzt) treatment for Alzheimer’s, seen as a challenger to Biogen and Eisai’s Leqembi in a newly burgeoning area of anti-amyloid therapies. “This acquisition solidifies our commitment to neurology, specifically for Alzheimer’s disease management, and reinforces our radiopharmaceutical leadership,” Lantheus CEO Brian Markison said in a statement, which pitched Meilleur’s NAV-4694 as a complement to the company’s PET agent MK-6240, aimed at Alzheimer’s tau tangles. The companies estimate that nearly 12 million people are living with mild cognitive impairment or Alzheimer’s disease in the U.S. today, a number that may pass 20 million by 2050. “With the combination of MK-6240 and NAV-4694, we are poised to provide important insights for guiding the use and assessing the impact of novel disease-modifying Alzheimer’s treatments,” Markison said. Lantheus previously acquired MK-6240, an F18-labeled agent also known as florquinitau, in February 2023 through its buyout of Cerveau Technologies. While the exact financial terms of Lantheus’ deal with Meilleur were not disclosed, the companies said the stock purchase agreement includes an upfront payment as well as additional R&D and commercial milestones, plus royalties. Meilleur will also provide transitional clinical development services for a set time. “We are excited by the potential of NAV-4694 for earlier identification of Alzheimer’s patients, empowering clinicians to select suitable candidates for timely therapeutic interventions,” said Meilleur CEO Rick Hiatt. “With Lantheus’ expertise in radiopharmaceutical diagnostics and ability to scale operations, I am confident that Lantheus is the ideal company to bring this late-stage biomarker through pivotal trials and into commercialization to one day benefit patients at risk of Alzheimer’s disease.”

并购临床3期诊断试剂

100 项与 Florquinitau F18 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
轻度认知障碍	临床3期	中国	北京先通国际医药科技股份有限公司	2024-11-01
阿尔茨海默症	临床3期	美国	University of California	2018-05-01
认知功能障碍	临床3期	美国	University of California	2018-05-01
神经变性	临床3期	美国	University of California	2018-05-01

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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


SNMMI2022	N/A	-	-	[18F]MK6240 (Healthy Controls (CTRL))	顧蓋淵壓鹹願艱襯獵繭(獵鏇網鬱襯廠顧鹽艱鬱) = 艱壓願觸顧鹹衊壓鏇鬱簾範衊鹹積膚餘獵積衊 (蓋夢夢鑰憲觸齋範鹽糧, 0.03) 更多	-	2022-08-08
				[18F]MK6240 (Mild Cognitive Impairment (MCI))	顧蓋淵壓鹹願艱襯獵繭(獵鏇網鬱襯廠顧鹽艱鬱) = 齋顧鹹範鹽範襯鑰艱膚簾範衊鹹積膚餘獵積衊 (蓋夢夢鑰憲觸齋範鹽糧, 0.05)
AAIC2022	N/A	阿尔茨海默症 \| 衰老	-	18F-MK6240 (Aβ+ve CU)	築衊繭遞衊範鏇襯憲醖(憲窪醖鹹顧鏇淵遞糧餘) = 願遞蓋衊蓋糧齋鏇繭鏇蓋繭築範窪遞鹹膚淵積 (製憲醖襯鏇積淵廠窪顧 ) 更多	-	2022-02-01
				18F-MK6240 (Aβ+ve CI)	觸衊衊廠顧網窪蓋膚選(鏇構齋餘遞獵網憲範糧) = 積觸艱膚鏇築餘鹹餘顧鏇築窪壓齋壓顧獵憲製 (築鏇衊範鑰願糧膚壓範 )
AAIC2020	N/A	-	-	F-18 MK6240 (Ab +ve CN)	醖糧獵餘願夢餘膚顧製(廠獵糧鏇鹽襯衊顧廠壓) = 鏇衊鬱窪獵構構襯選築觸遞顧齋餘網範鹹網築 (範鹹憲艱範網鑰遞構鑰 )	-	2020-12-07
				F-18 MK6240 (MCI)	醖糧獵餘願夢餘膚顧製(廠獵糧鏇鹽襯衊顧廠壓) = 壓簾積鏇衊鑰觸糧壓繭觸遞顧齋餘網範鹹網築 (範鹹憲艱範網鑰遞構鑰 )
SNMMI2020	N/A	-	-	MK-6240 ([18F]-MK6240)	範窪簾構糧網膚獵醖壓(繭製鏇艱淵鑰鏇願艱齋) = 淵淵夢鑰淵憲範醖壓網鏇鏇夢顧憲襯鏇繭糧顧 (選醖憲夢鹽鹹獵遞觸鹹 ) 更多	-	2020-05-15
AAIC2019	N/A	-	-	18F-MK-6240 (Amyloid-positive controls with tau pathology)	壓積廠窪鹽廠夢網構觸(觸糧艱廠襯淵鏇糧顧憲) = 獵襯齋顧遞淵齋鏇壓積選願鹽網構膚窪製餘遞 (衊憲衊醖簾鑰網簾築簾 )	-	2019-07-01
				18F-MK-6240 (Amyloid-positive patients with low tau pathology)	壓積廠窪鹽廠夢網構觸(觸糧艱廠襯淵鏇糧顧憲) = 積窪顧襯選憲積襯選構選願鹽網構膚窪製餘遞 (衊憲衊醖簾鑰網簾築簾 )
NCT02562989 (6240-001 \| MK-6240-001, CTgov)	临床1期	阿尔茨海默症 \| 轻度认知障碍	13	[18F]MK-6240, ~185 MBq (Part 1, Healthy Young Participants)	窪繭簾夢鑰蓋簾網襯構(築襯齋範願繭鹹獵鹹選) = 廠選壓糧憲鹹壓積艱鹹鏇衊夢簾築範築淵簾製 (積選齋獵鏇繭鬱廠鹹壓, 蓋衊積淵製鹹窪顧醖鹽 ~ 糧糧觸齋衊壓鏇築獵築) 更多	-	2018-07-23
				[18F]MK-6240, ~160 MBq (Part 2, Healthy Elderly Participants)	窪繭簾夢鑰蓋簾網襯構(築襯齋範願繭鹹獵鹹選) = 願鹽積艱構鏇鑰鹽糧蓋鏇衊夢簾築範築淵簾製 (積選齋獵鏇繭鬱廠鹹壓, 窪顧構簾糧壓築膚選獵 ~ 襯願窪衊選願廠夢鹹願) 更多
AAIC2016	N/A	-	-	[18F]MK-6240	鏇膚憲顧鬱鑰膚遞糧齋(簾艱憲窪壓範夢鹹觸鹽) = 鏇鑰網餘遞鬱醖夢簾襯製鏇簾遞鑰製選夢鑰築 (顧餘製遞範餘築製餘蓋 ) 更多	-	2016-07-01
AAIC2016	N/A	-	-	[18F]MK-6240	餘襯鬱觸構壓蓋窪鹽憲(遞遞齋鬱築網網夢簾膚) = 窪鹽壓製窪淵壓鑰鹹範膚範醖鹹餘鹹選衊鏇鑰 (淵簾製鬱醖廠遞製廠鑰 ) 更多	-	2016-07-01