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| 1 | Development of ^(18)F-labeled radiotracers for neuroreceptor imaging with positron emission tomography显示文摘Positron emission tomography(PET)is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases.PET uses biomolecules as probes which are labeled with radionuclides of short half-lives,synthesized prior to the imaging studies.These probes are called radiotracers.Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min.The delivery of such radiotracers into the brain provides images of transport,metabolic,and neurotransmission processes on the molecular level.After a short introduction into the principles of PET,this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application.Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases,but also allow molecular neuroreceptor imaging studies in various small-animal models of disease,including geneticallyengineered animals.Furthermore,they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets,to investigate pathophysiology,to discover potential drug candidates,and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo. | Peter Brust Jrg van den Hoff Jrg Steinbach | 2014 | Neuroscience Bulletin2014，30，5： | 3 |
| 2 | 新的^(99m)Tc标记σ受体肿瘤显像剂显示文摘采用整体法设计合成了新的99mTc标记的配合物[N-[2-((2-oxo-2-(4-(3-phenylpropyl)piperazin-1-yl)ethyl)(2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato]technetium(Ⅴ)oxide(PPPE-MAMA′-99mTcO)([99mTc]-2)及其相应的铼配合物(PPPE-MAMA′-ReO)(Re-2).竞争结合实验表明Re-2对σ1和σ2受体有中等亲和力,Ki值分别为8.67±0.07和5.71±1.88μmol/L;荷MCF-7人乳癌裸鼠尾静脉注射[99mTc]-2后0.5h,4h,20h采集平面图像,20h时可以看到肿瘤部位有放射性浓集,共同注射[99mTc]-2和抑制剂氟哌啶醇(1mg/kg)后显像,20h时肿瘤部位无明显放射性浓集;体内生物分布结果显示,注射后24h肿瘤中的放射性摄取为0.14%±0.01%ID/g,肿瘤/肌肉比为6.02±0.87.上述结果表明:虽然用整体设计法对前体化合物的结构进行了较大修饰,但得到的99mTc-配合物([99mTc]-2)在肿瘤内仍有一定的浓集,与σ1和σ2受体仍保持一定的亲和力.在此配合物的基础上,对其进行进一步的结构修饰有可能得到对σ受体亲和力更高的肿瘤显像剂. | 樊彩云 贾红梅 Deuther-Conrad Winnie Brust Peter Steinbach Jrg 刘伯里 | 2005 | 中国科学(B辑)2005，35，6： | 1 |
| 3 | Acetylcholine receptors in dementia and mild cognitive impairment显示文摘 | Osama Sabri Kai Kendziorra Henrike Wolf Hermann-Josef Gertz Peter Brust | 2008 | European Journal of Nuclear Medicine and Molecular Imaging2008，，： | 1 |
| 4 | Acetylcholine receptors in dementia and mild cognitive impairment显示文摘 | Osama Sabri Kai Kendziorra Henrike Wolf Hermann-Josef Gertz Peter Brust | 2008 | European Journal of Nuclear Medicine and Molecular Imaging2008，，1： | 1 |
| 5 | Functional expression of the serotonin transporter in immortalized rat brain microvessel endothelial cells显示文摘 | Anne Friedrich Istvan A Krizbai | 2000 | Journal of Neurochemistry2000，74，3： | 1 |
| 6 | Enantioseparation of vesamicol and novel vesamicol analogs byhigh-performance liquid chromatography on different chiralstationary phases显示文摘 | Barbara Wenzel Steffen Fischer Peter Brust | 2010 | Journal of Chromatography A2010，1217，： | 1 |
| 7 | Quality and eco- nomies: five key issues显示文摘 | PETER J BRUST FRANK M GRYNA | 2002 | Quality Progress2002，，10： | 1 |
| 8 | Synthesis and in vitro evaluation of new diphenyl ether derivatives as serotonin transporter ligands显示文摘For the development of new ligands as potential imaging agents for the serotonin transporter (SERT),a series of diphenyl ether derivatives have been synthesized,characterized,and evaluated for their in vitro binding affinities to the SERT. Among the above compounds,2-(2-((dimethylamino)methyl)-4-fluoro-phenoxy)-5-bromobenzenamine (15) and 2-(2-((dimethylamino)methyl)-4-fluorophenoxy)-5-iodobenzene amine (16) show high binding affinities for the SERT with Ki values of 0.28 and 0.20 nmol·L-1,respectively. They can be further labeled with carbon-11,fluorine-18,iodine-123 or bromine-76,and evaluated as useful imaging agents for the SERT. Moreover,the study of the structure-activity relationship (SAR) provides some useful information for the future design of new ligands. | DEUTHER-CONRAD Winnie BRUST Peter STEINBACH Jrg VERCOUILLIE Johnny | 2008 | Science China Chemistry2008，51，5： | 0 |
| 9 | 新的五羟色胺转运蛋白二芳基醚类衍生物配体的合成与体外评价显示文摘为开发新的配体作为有潜力的五羟色胺转运蛋白(SERT)显像剂,合成了一系列二芳基醚类衍生物,并对这些化合物进行了表征,测定了对SERT的体外亲和性.其中,化合物2-(2-((dimethylamino)methyl)-4-fluorophenoxy)-5-bromobenzeneamine(15)和2-(2-((dimethyl-amino)-methyl)-4-fluorophenoxy)-5-iodobenzeneamine(16)表现出最高的亲和性,Ki分别为0.28和0.20nmol·L?1.它们可以用碳-11、氟-18、碘-123或者溴-76进一步标记,进而评价作为SERT显像剂的可能性.而且,构效关系的研究为将来设计新的配体提供了一些有用的信息. | 郭运行 陈祥纪 贾红梅 DEUTHER-CONRAD Winnie BRUST Peter STEINBACH Jorg VERCOUILLIE Johnny 刘伯里 | 2008 | 中国科学(B辑)2008，38，2： | 0 |
| 10 | Discovery and development of brain-penetrant ^(18)F-labeled radioligands for neuroimaging of the sigma-2 receptors显示文摘We have discovered and synthesized a series of indole-based derivatives as novel sigma-2(σ_(2))receptor ligands.Two ligands with high σ_(2) receptor affinity and subtype selectivity were then radiolabeled with F-18 in good radiochemical yields and purities,and evaluated in rodents.In biodistribution studies in male ICR mice,radioligand[18F]9,or 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-4-(2-[18F]fluoroethoxy)-1H-indole,was found to display high brain uptake and high brain-to-blood ratio.Pretreatment of animals with the selective σ_(2) receptor ligand CM398 led to significant reductions in both brain uptake(29%-54%)and brain-to-blood ratio(60%-88%)of the radioligand in a dose-dependent manner,indicating high and saturable specific binding of[18F]9 to σ_(2) receptors in the brain.Further,ex vivo autoradiography in male ICR mice demonstrated regionally heterogeneous specific binding of[18F]9 in the brain that is consistent with the distribution pattern of σ_(2) receptors.Dynamic positron emission tomography imaging confirmed regionally distinct distribution and high levels of specific binding for[18F]9 in the rat brain,along with appropriate tissue kinetics.Taken together,results from our current study indicated the novel radioligand[18F]9 as the first highly specific and promising imaging agent for σ_(2) receptors in the brain. | Ying Zhang Tao Wang Xiaojun Zhang Winnie Deuther-Conrad Hualong Fu Mengchao Cui Jinming Zhang Peter Brust Yiyun Huang Hongmei Jia | 2022 | Acta Pharmaceutica Sinica B2022，12，3： | 0 |
| 11 | Synthesis and characterization of the two enantiomers of a chiral sigma-1 receptor radioligand:(S)-(+)-and(R)-(-)-[^(18)F]FBFP显示文摘Racemic[^(18)F]FBFP([^(18)F]1)proved to be a potentσ_(1) receptor radiotracer with superior imaging properties.The pure enantiomers of unlabeled compounds(S)-and(R)-1 and the corresponding iodonium ylide precursors were synthesized and characterized.The two enantiomers(S)-1 and(R)-1 exhibited comparable high affinity forσ_(1) receptors and selectivity overσ_(2) receptors.The Ca^(2+) fluorescence assay indicated that(R)-1 behaved as an antagonist and(S)-1 as an agonist forσ_(1) receptors.The ^(18)F-labeled enantiomers(S)-and(R)-[^(18)F]1 were obtained in>99%enantiomeric purity from the corresponding enantiopure iodonium ylide precursors with radiochemical yield of 24.4%±2.6%and molar activity of 86–214 GBq/μmol.In ICR mice both(S)-and(R)-[^(18)F]1displayed comparable high brain uptake,brain-to-blood ratio,in vivo stability and binding specificity in the brain and peripheral organs.In micro-positron emission tomography(PET)imaging studies in rats,(S)-[^(18)F]1 exhibited faster clearance from the brain than(R)-[^(18)F]1,indicating different brain kinetics of the two enantiomers.Both(S)-and(R)-[^(18)F]1 warrant further evaluation in primates to translate a single enantiomer with more suitable kinetics for imaging theσ_(1) receptors in humans. | Tao Wang Ying Zhang Xiaojun Zhang Leyuan Chen Mingqiang Zheng Jinming Zhang Peter Brust Winnie Deuther-Conrad Yiyun Huang Hongmei Jia | 2022 | Chinese Chemical Letters2022，33，7： | 0 |
| 12 | ^(123)Ⅰ和^(99)Tc^m标记的吲哚类σ_2受体放射性示踪剂的设计、稳定化合物的合成及体外生物评价显示文摘设计了123Ⅰ和99Tcm标记的吲哚类σ2受体肿瘤放射性示踪剂,合成了其稳定化合物(Indole-Ⅰ和Indole-MAMA-Re)和标记前体(Indole-MAMA)。体外受体结合分析结果表明,化合物Indole-Ⅰ对σ1和σ2受体的抑制常数Ki值分别为(0.574±0.355)μmol/L和(0.162±0.030)μmol/L(n=3),Indole-MAMA-Re对σ1和σ2受体的抑制常数Ki值分别为(3.75±2.22)μmol/L和(7.83±4.87)μmol/L(n=3)。成功制备了99Tcm-Indole-MAMA,纯化后经高效液相色谱法(HPLC)分析其放化纯大于90%。今后可在本文化合物的基础上通过结构优化,设计合成对σ2受体具有高亲和力和选择性的吲哚类SPECT肿瘤显像剂。 | 李艳 贾红梅 Deuther-Conrad Winnie Brust Peter Steinbach Joerg 刘伯里 | 2010 | 核化学与放射化学2010，32，2： | 0 |
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