氚[3H]-NS10743(Tritium [3h ]-NS10743) - 药物靶点：CHRNA7_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

诊断用放射药物

别名

3H NS10743、3H-NS10743、3HNS10743

+ [3]

靶点

CHRNA7

作用方式

调节剂

作用机制

α7 receptor调节剂(神经性乙酰胆碱受体蛋白α-7亚基调节剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

DanPET AB

在研机构

DanPET AB

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与氚[3H]-NS10743 相关的临床结果

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100 项与氚[3H]-NS10743 相关的转化医学

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100 项与氚[3H]-NS10743 相关的专利（医药）

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3

项与氚[3H]-NS10743 相关的文献（医药）

2015-01-01·Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine3区 · 工程技术

A high-yield automated radiosynthesis of the alpha-7 nicotinic receptor radioligand [18F]NS10743

3区 · 工程技术

Article

作者: Fischer, Steffen ; Deuther-Conrad, Winnie ; Wenzel, Barbara ; Teodoro, Rodrigo ; Oh-Nishi, Arata ; Brust, Peter ; Suhara, Tetsuya ; Peters, Dan

[¹⁸F]NS10743, a promising and highly competitive α7 nAChR radioligand has been synthesized so far by microwave irradiation using a manual single-mode device followed by a palladium-catalyzed reduction of remaining nitro-precursor for HPLC separation purposes. For further preclinical and clinical use, regulated production of [¹⁸F]NS10743 by fully automated radiosynthesis is a crucial requirement. Therefore, we chose a commercial synthesis module and developed the automated radiosynthesis of [¹⁸F]NS10743. Besides evaluation of several radiosynthesis procedures, we performed an extensive HPLC study for quantitative separation of [¹⁸F]NS10743 from the corresponding nitro precursor. After implementation of the optimized procedure on a TRACERlab^TM FX F-N synthesis module, [¹⁸F]NS10743 was obtained in high radiochemical purity (≥99%) with an overall radiochemical yield of 32.2±7% (n=3). The specific activities at the end of the synthesis were 571±17GBq/µmol (n=3).

2011-08-01·European Journal of Nuclear Medicine and Molecular Imaging

Assessment of α7 nicotinic acetylcholine receptor availability in juvenile pig brain with [18F]NS10743

Article

作者: Brust, Peter ; Hiller, Achim ; Peters, Dan ; Funke, Uta ; Fischer, Steffen ; Becker, Georg ; Xiong, Guoming ; Cumming, Paul ; Deuther-Conrad, Winnie ; Sabri, Osama

PURPOSE:

To conduct a quantitative PET assessment of the specific binding sites in the brain of juvenile pigs for [(18)F]NS10743, a novel diazabicyclononane derivative targeting α7 nicotinic acetylcholine receptors (α7 nAChRs).

METHODS:

Dynamic PET recordings were made in isoflurane-anaesthetized juvenile pigs during 120 min after administration of [(18)F]NS10743 under baseline conditions (n = 3) and after blocking of the α7 nAChR with NS6740 (3 mg·kg(-1) bolus + 1 mg·kg(-1)·h(-1) continuous infusion; n = 3). Arterial plasma samples were collected for determining the input function of the unmetabolized tracer. Kinetic analysis of regional brain time-radioactivity curves was performed, and parametric maps were calculated relative to arterial input.

RESULTS:

Plasma [(18)F]NS10743 passed readily into the brain, with peak uptake occurring in α7 nAChR-expressing brain regions such as the colliculi, thalamus, temporal lobe and hippocampus. The highest SUV(max) was approximately 2.3, whereas the lowest uptake was in the olfactory bulb (SUV(max) 1.53 ± 0.32). Administration of NS6740 significantly decreased [(18)F]NS10743 binding late in the emission recording throughout the brain, except in the olfactory bulb, which was therefore chosen as reference region for calculation of BP(ND). The baseline BP(ND) ranged from 0.39 ± 0.08 in the cerebellum to 0.76 ± 0.07 in the temporal lobe. Pretreatment and constant infusion with NS6740 significantly reduced the BP(ND) in regions with high [(18)F]NS10743 binding (temporal lobe -29%, p = 0.01; midbrain: -35%, p = 0.02), without significantly altering the BP(ND) in low binding regions (cerebellum: -16%, p = 0.2).

CONCLUSION:

This study confirms the potential of [(18)F]NS10743 as a target-specific radiotracer for the molecular imaging of central α7 nAChRs by PET.

2009-05-01·European Journal of Nuclear Medicine and Molecular Imaging

Molecular imaging of α7 nicotinic acetylcholine receptors: design and evaluation of the potent radioligand [18F]NS10743

Article

作者: Peters, Dan ; Hiller, Achim ; Fischer, Steffen ; Steinbach, Joerg ; Brunicardi Timmermann, Daniel ; Ostergaard Nielsen, Elsebet ; Brust, Peter ; Deuther-Conrad, Winnie ; Sabri, Osama

PURPOSE:

The outstanding diversity of cellular properties mediated by neuronal and nonneuronal alpha7 nicotinic acetylcholine receptors (alpha7 nAChR) points to the diagnostic potential of quantitative nuclear molecular imaging of alpha7 nAChR in neurology and oncology. It was our goal to radiolabel the alpha7 nAChR agonist 4-[5-(4-fluoro-phenyl)-[1,3,4]oxadiazol-2-yl]-1,4-diaza-bicyclo[3.2.2]nonane (NS10743) and to assess the selectivity of [(18)F]NS10743 binding site occupancy in animal experiments.

METHODS:

[(18)F]NS10743 was synthesized by nucleophilic substitution of the nitro precursor. In vitro receptor affinity and selectivity were assessed by radioligand competition and autoradiography. The radiotracer properties were evaluated in female CD-1 mice by brain autoradiography and organ distribution. Target specificity was validated after treatment with SSR180711 (10 mg/kg, intraperitoneal), and metabolic stability was investigated using radio-HPLC.

RESULTS:

The specific activity of [(18)F]NS10743 exceeded 150 GBq/micromol at a radiochemical purity >99%. In vitro, NS10743 and [(18)F]NS10743 showed high affinity and specificity towards alpha7 nAChR. The brain permeation of [(18)F]NS10743 was fast and sufficient with values of 4.83 and 1.60% injected dose per gram and brain to plasma ratios of 3.83 and 2.05 at 5 and 60 min after radiotracer administration. Brain autoradiography and organ distribution showed target-specific accumulation of [(18)F]NS10743 in brain substructures and various alpha7 nAChR-expressing organs. The radiotracer showed a high metabolic stability in vivo with a single polar radiometabolite, which did not cross the blood-brain barrier.

CONCLUSION:

The good in vitro and in vivo features of [(18)F]NS10743 make this radioligand a promising candidate for quantitative in vivo imaging of alpha7 nAChR expression and encourage further investigations.

100 项与氚[3H]-NS10743 相关的药物交易

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