Non-inferiority study of the molecular imaging of dopamine transporters using [123I]-FP/CIT-SPECT and [18F] LBT-999-PET to distinguish between Parkinson’s Disease and Essential Tremor. - DATTEP

开始日期2021-03-31

申办/合作机构

Zionexa US Corp.

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

CTIS2023-504893-39-00

/ Not yet recruiting临床2/3期IIT

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

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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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 imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of...4区 · 医学

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

4区 · 医学

Article

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

BACKGROUND:

The 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.

METHODS:

After 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).

RESULTS:

No 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.

CONCLUSIONS:

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

Abstract:

Background:

Fluorine 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.

Results:

Automation 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.

Conclusion:

Both 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.

2019-01-01·American journal of analytical chemistry

Development of a Fast and Facile Analytical Approach to Quantify Radiometabolites in Human Plasma Samples Using Ultra High Performance Liquid Chromatography

作者: Guilloteau, Denis ; Vercouillie, Johnny ; Netter, Claude ; Bidault, Rudy ; Arlicot, Nicolas ; Malherbe, Cecile

Introduction: Conventional metabolite analyses often require manual sample preparation, generating variability of measurements.This study describes a new method to quantify radiometabolites in blood, combining ultra high performance liquid chromatog. (UHPLC) and turbulent flow chromatog., an alternative fully automated process allowing analyte's extractionMethods: A new radiotracer for dopamine transporter imaging, namely LBT-999, was used to demonstrate the method's robustness.Radiodetector sensitivity and preliminary evaluation were resp. determined by anal. of calibrated samples of [18F]LBT-999 and blood samples from 4 healthy subjects injected with [18F]LBT-999, withdrawn at 5, 15, 30 and 45 min pi.Results: With three sequential loadings (3 × 100μL) of the Turboflow column, mean coefficients of variation were 1%, below 2%, 2% and 30.9% for matrix effect, specificity, repeatability and intermediate precision, resp.Retention times for [18F]LBT-999 and the two radiometabolites detected by radio-UHPLC were 6.5, 4.8 and 9.6 min.Forty-five min after the injection, parent fraction was still predominant with 57.8% ± 25% of the total radioactivity.Conclusions: An innovative approach, allying UHPLC and Turboflow column, was developed and its sensitivity, linearity, specificity and repeatability validated.Preliminary results of the clin. trial are in accordance with literature data, demonstrating its efficiency in radiometabolites quantification.

100 项与 Fluorine 18 LBT 999(INSERM) 相关的药物交易

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