Fluorine 18 LBT 999(INSERM)(Fluorine 18 LBT 999(INSERM)) - 药物靶点：DAT_在研适应症：诊断试剂_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

+ [3]

靶点

DAT

作用机制

DAT拮抗剂(多巴胺转运体拮抗剂)、PET imaging(正电子发射断层成像术增强剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构-

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C20H26FNO2

InChIKeyXZWRXMFAFBSAJC-INCYSKAQSA-N

CAS号940949-46-2

关联

2

项与 Fluorine 18 LBT 999(INSERM) 相关的临床试验

CTIS2023-504893-39-00 / Not yet recruitingIIT

Dopaminergic disruption induced by traumatic coma: multimodal neuroimaging approaches to characterize dopaminergic pathways abnormalities and biomarkers of recovery using the [18F]LBT-999 radiotracer. - C22-62

开始日期-

申办/合作机构

Institut National de la Santé et de la Recherche Médicale

NCT02393027 / Terminated早期临床1期IIT

Quantification of Dopamine Active Transporter (DAT) in Humans: Validation of a New Radiophamaceutical, the [18F] LBT-999

Idiopathic Parkinson's disease (IPD) is a degenerative disease affecting the dopaminergic system. Clinical symptoms of IPD commonly begin after the loss of at least 40 to 50% of striatal dopaminergic terminals (specially putaminal terminals).
The Dopamine neuronal transporter (DAT) is a highly expressed protein in the membrane of presynaptic nigrostriatal dopaminergic terminals. The use of a DAT's radioligand in the initial stages of the disease would lead to an early detection of nigral cell loss.
Currently, only one DAT's radioligand has obtained marketing authorization in France, the 123I-FPCIT, for use in Single Photon Emission Computed Tomography (SPECT).
Otherwise, the Positron Emission Tomography (PET), a more sensitive technology than SPECT with higher resolution has become for a few years the new gold standard for visual analysis and quantification of neurotransmission systems (including the dopaminergic system).
A DAT tracer labelled with Carbon 11 ([11C] PE2l) have been developed and is currently used as a reference in various research centers.
However, in order to enable a clinical use of this tracer (which currently can't be because of the too short period of Carbon 11), the unit INSERM U930 "Imaging and Brain" in collaboration with the CERRP (Center for Studies and Research on Radiopharmaceuticals) developed a new version of this tracer, labelled with 18-fluor: the [18F] LBT-999.
The main goal of this study is to compare the [18F] LBT-999 uptake between a group of patients suffering from a Parkinsonien syndrome to a group healthy volunteers.

开始日期2015-03-01

申办/合作机构

University Hospitals of Tours

100 项与 Fluorine 18 LBT 999(INSERM) 相关的临床结果

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100 项与 Fluorine 18 LBT 999(INSERM) 相关的转化医学

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100 项与 Fluorine 18 LBT 999(INSERM) 相关的专利（医药）

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13

项与 Fluorine 18 LBT 999(INSERM) 相关的文献（医药）

2022-05-01·The Quarterly Journal of Nuclear Medicine and Molecular Imaging4区 · 医学

Imaging of dopamine transporter with [18F]LBT-999: initial evaluation in healthy volunteers

4区 · 医学

Article

作者: Deloye, Jean-Bernard ; Vercouillie, Johnny ; Malherbe, Cécile ; Bidault, Rudy ; Maia, Serge ; Barantin, Laurent ; Ribeiro, Maria-Joao ; Guilloteau, Denis ; Gissot, Valérie ; Cottier, Jean-Philippe ; Arlicot, Nicolas

BACKGROUNDThe aim of this study was to evaluate in healthy human brain the distribution, uptake, and kinetics of [¹⁸F]LBT-999, a PET ligand targeting the dopamine transporter, to assess its ability to explore dopaminergic innervation, using a shorter protocol, more convenient for patients than currently with [¹²³I]ioflupane.METHODSAfter intravenous injection of [¹⁸F]LBT-999, 8 healthy subjects (53-80y) underwent a dynamic PET-scan. Venous samples were concomitantly obtained for metabolites analysis. Time activity curves (TACs) were generated for several ROIs (caudate, putamen, occipital cortex, substantia nigra and cerebellum). Cerebellum was used as reference region to calculate binding potentials (BPND).RESULTSNo adverse events or detectable pharmacological effects were reported. [¹⁸F]LBT-999 PET revealed a good cerebral distribution, with an intense and symmetric uptake in both putamen and caudate (BPND of 6.75±1.17 and 6.30±1.17, respectively), without other brain abnormal tracer accumulation. Regional TACs showed a plateau from the maximal uptake, 20min pi, to the end of the acquisition for both caudate and putamen, whereas uptake in substantia nigra decreased progressively. A faster clearance and lowest BPND values were observed in both cortex and cerebellum. Ratios to the cerebellum exhibit value of about 3 in substantia nigra, close to 10 for both caudate and putamen, and remained around the value of 1 in cortex. The parent fraction of [¹⁸F]LBT-999 in plasma was 80%, 60% and 45% at 15, 30 and 45 min pi, respectively.CONCLUSIONSThese findings support the usefulness of [¹⁸F]LBT-999 for a quantitative clinical evaluation of presynaptic dopaminergic innervation.

2020-12-01·EJNMMI Radiopharmacy and Chemistry

Fully automated radiosynthesis of [18F]LBT999 on TRACERlab FXFN and AllinOne modules, a PET radiopharmaceutical for imaging the dopamine transporter in human brain

Article

作者: Bouvet, Yann ; Chicheri, Gabrielle ; Mothes, Céline ; Magadur, Pauline ; Emond, Patrick ; Arlicot, Nicolas ; Maia, Serge ; Viot, Gilles ; Dupont, Anne-Claire ; Deloye, Jean-Bernard ; Vala, Christine ; Vercouillie, Johnny ; Guilloteau, Denis

AbstractBackgroundFluorine labelled 8-((E)-4-fluoro-but-2-enyl)-3β-p-tolyl-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid methyl ester ([18F]LBT999) is a selective radioligand for the in vivo neuroimaging and quantification of the dopamine transporter by Positron Emission Tomography (PET). [18F]LBT999 was produced on a TRACERlab FXFN for the Phase I study but for Phase III and a potent industrial production transfer, production was also implemented on an AllinOne (AIO) system requiring a single use cassette. Both production methods are reported herein.ResultsAutomation of [18F]LBT999 radiosynthesis on FXFN was carried out in 35% yield (decay-corrected) in 65 min (n = 16), with a radiochemical purity higher than 99% and a molar activity of 158 GBq/μmol at the end of synthesis. The transfer to the AIO platform followed by optimizations allowed the production of [18F]LBT999 in 32.7% yield (decay-corrected) within 48 min (n = 5), with a radiochemical purity better than 98% and a molar activity above 154 GBq/μmol on average at the end of synthesis. Quality controls of both methods met the specification for clinical application.ConclusionBoth modules allow efficient and reproducible radiosynthesis of [18F]LBT999 with good radiochemical yields and a reasonable synthesis time. The developments made on AIO, such as its ability to meet pharmaceutical criteria and to more easily comply with GMP requirements, make it an optimal approach for the potent industrial production of [18F]LBT999 and future wider use.

2014-01-01·Nuclear Medicine and Biology4区 · 医学

In vivo PET quantification of the dopamine transporter in rat brain with [18F]LBT-999

4区 · 医学

Article

作者: Johnny Vercouillie ; Sylvie Chalon ; Jean-Bernard Deloye ; Denis Guilloteau ; Laurent Galineau ; Lucette Garreau ; Sophie Sérrière ; Clovis Tauber

INTRODUCTIONWe examined whether [(18)F]LBT-999 ((E)-N-(4-fluorobut-2-enyl)2β-carbomethoxy-3β-(4'-tolyl)nortropane) is an efficient positron emission tomography (PET) tracer for the quantification of the dopamine transporter (DAT) in the healthy rat brain.METHODSPET studies were performed using several experimental designs, i.e. test-retest, co-injection with different doses of unlabelled LBT, displacement with GBR12909 and pre-injection of amphetamine.RESULTSThe uptake of [(18)F]LBT-999 confirmed its specific binding to the DAT. The non-displaceable uptake (BP(ND)) in the striatum, between 5.37 and 4.39, was highly reproducible and reliable, and was decreased by 90% by acute injection of GBR12909. In the substantia nigra/ventral tegmental area (SN/VTA), the variability was higher and the reliability was lower. Pre-injection of amphetamine induced decrease of [(18)F]LBT-999 BP(ND) of 50% in the striatum.CONCLUSIONS[(18)F]LBT-999 allows the quantification of the DAT in living rat brain with high reproducibility, sensitivity and specificity. It could be used to quantify the DAT in rodent models, thereby allowing to study neurodegenerative and neuropsychiatric diseases.

100 项与 Fluorine 18 LBT 999(INSERM) 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
诊断试剂	临床3期	-	Atos SE	-
诊断试剂	临床3期	-	Cyclopharm Ltd.	-
诊断试剂	临床3期	-	Zionexa SAS	-
特发性震颤	临床前	-	Zionexa SAS	2020-05-01
帕金森病	临床前	法国	Zionexa SAS	2019-05-26