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Recent developments on PET radiotracers for TSPO and their applications in neuroimaging

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Acta Pharmaceutica Sinica B 2021年第2期11卷 373-393页

作者： Lingling zhang Kuan Hu Tuo Shao Lu Hou shaojuan zhang Weijian Ye Lee Josephson Jeffrey H.Meyer Ming-Rong zhang Neil Vasdev Jinghao Wang Hao Xu Lu Wang Steven H.Liang Center of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine and PET/CT-MRI CenterThe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Department of Neurology the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Department of Radiopharmaceuticals Development National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChiba 263-8555Japan Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital&Department of RadiologyHarvard Medical SchoolBostonMA 02114USA Azrieli Centre for Neuro-Radiochemistry Brain Health Imaging CentreCentre for Addiction and Mental Health&Department of PsychiatryUniversity of TorontoToronto ON M5T 1R8Canada Department of Pharmacy the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China

The 18 kDa translocator protein(TSPO),previously known as the peripheral benzodiazepine receptor,is predominately localized to the outer mitochondrial membrane in steroidogenic *** TSPO expression is relatively low under physiological conditions,but is upregulated in response to glial cell *** the primary index of neuroinflammation,TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases,including Alzheimer’s disease(AD),amyotrophic lateral sclerosis(ALS),Parkinson’s disease(PD),multiple sclerosis(MS),major depressive disorder(MDD)and obsessive compulsive disorder(OCD).In this context,numerous TSPO-targeted positron emission tomography(PET)tracers have been *** them,several radioligands have advanced to clinical research *** this review,we will overview the recent development of TSPO PET tracers,focusing on the radioligand design,radioisotope labeling,pharmacokinetics,and PET imaging ***,we will consider current limitations,as well as translational potential for future application of TSPO *** review aims to not only present the challenges in current TSPO PET imaging,but to also provide a new perspective on TSPO targeted PET tracer discovery *** these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.

关键词： TSPO Microglial activation Neuroinflammation Positron emission tomography(PET) CNS disorders

Discovery of a highly specific ^(18)F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1963-1975页

作者： Zhiwei Xiao Huiyi Wei Yi Xu Ahmed Haider Junjie Wei Shiyu Yuan Jian Rong Chunyu Zhao Guocong Li Weibin zhang Huangcan Chen Yuefeng Li Lingling zhang Jiyun Sun shaojuan zhang Hai-Bin Luo Sen Yan Qijun Cai Lu Hou Chao Che Steven H.Liang Lu Wang Center of Cyclotron and PET Radiopharmaceuticals Department of Nuclear Medicine and PET/CT-MRI Centerthe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital&Department of RadiologyHarvard Medical SchoolBostonMA 02114USA Department of Cardiology the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China State Key Laboratory of Chemical Oncogenomics Key Laboratory of Chemical GenomicsPeking University Shenzhen Graduate SchoolShenzhen 518055China Guangdong Landau Biotechnology Co.Ltd. Guangzhou 510555China Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikou 570228China Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhou 510632China

As a member of cyclic nucleotide phosphodiesterase(PDE)enzyme family,PDE10A is in charge of the degradation of cyclic adenosine(cAMP)and guanosine monophosphates(cGMP).While PDE10A is primarily expressed in the medium spiny neurons of the striatum,it has been implicated in a variety of neurological ***,inhibition of PDE10A has proven to be of potential use for the treatment of central nervous system(CNS)pathologies caused by dysfunction of the basal ganglia–of which the striatum constitutes the largest component.A PDE10A-targeted positron emission tomography(PET)radioligand would enable a better assessment of the pathophysiologic role of PDE10A,as well as confirm the relationship between target occupancy and administrated dose of a given drug candidate,thus accelerating the development of effective PDE10A *** this study,we designed and synthesized a novel ^(18)F-aryl PDE10A PET radioligand,codenamed[^(18)F]P10A-1910([^(18)F]9),in high radiochemical yield and molar activity via spirocyclic iodonium ylide-mediated radiofluorination.[^(18)F]9 possessed good in vitro binding affinity(IC_(50)=2.1 nmol/L)and selectivity towards ***,[^(18)F]9 exhibited reasonable lipophilicity(logD=3.50)and brain permeability(P_(app)>10×10^(−6) cm/s in MDCK-MDR1 cells).PET imaging studies of[^(18)F]9 revealed high striatal uptake and excellent in vivo specificity with reversible tracer *** studies in rodents revealed an improved plasma and brain stability of[^(18)F]9 when compared to the current reference standard for PDE10A-targeted PET,[^(18)F]***,dose–response experiments with a series of escalating doses of PDE10A inhibitor 1 in rhesus monkey brains confirmed the utility of[^(18)F]9 for evaluating target occupancy in vivo in higher *** conclusion,our results indicated that[^(18)F]9 is a promising PDE10A PET radioligand for clinical translation.

关键词： Phosphodiesterase 10A PET radioligand 18F Spirocyclic iodonium ylide Nonhuman primate Target occupancy

Apparent diffusion coefficient in normal and abnormal pattern of intervertebral lumbar discs: initial experience

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The Journal of Biomedical Research 2011年第3期25卷 197-203页

作者： Gang Niu Xuewen Yu Jian Yang Rong Wang shaojuan zhang Youmin Guo Department of Diagnostic Radiology the First Hospital of Medical School Xi'an Jiaotong University Xi'an Shaanxi 710061 China

The aim of the present study was to compare the relationship of morphologically defined non-bulging/herni-ated, bulging and herniated intervertebral lumbar discs with quantitative apparent diffusion coefficient （ADC）. Thirty-two healthy volunteers and 28 patients with back pain or sciatica were examined by MRI. All intervertebral lumbar discs from L1 to S1 were classified according to morphological abnormality and degenerated grades. The ADC values of nucleus pulposus （NP） were measured and recorded. The significant differences about mean ADC values of NP were found between non-bulging/herniated discs and bulging discs as well as herniated discs （P 0.05）, whereas there were no significant differences in ADC values between bulging and herniated discs （P 0.05）. Moreover, statistically significant relationship was found in the mean ADC values of NP between ＂non-bulging/herniated and non-degenerated discs＂ and ＂non-bulging/herniated degenerated discs＂ as well as herniated discs （P 0.05）. Linear regression analysis between ADC value and disc level revealed an inverse correlation （r = -0.18）. The ADC map of the NP is a potentially useful tool for the quantitative assessment of componential and molecular alterations accompanied with lumbar disc abnormalities.

关键词： intervertebral lumbar disc apparent diffusion coefficient disc bulging disc herniation

经导管主动脉瓣置换术治疗二叶式主动脉瓣狭窄与三叶式主动脉瓣狭窄疗效比较的meta分析

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临床心血管病杂志 2020年第11期36卷 1024-1029页

作者：郑五强祖秀光张少娟河北医科大学第二医院心内三科石家庄050000

目的:系统评价经导管主动脉瓣置换术治疗二叶式主动脉瓣狭窄与三叶式主动脉瓣狭窄的疗效。方法:检索建库至2020年2月PubMed、Embase、Cochrane图书馆、万方数据库和中国知网的随机对照及队列研究试验,同时采用Revman 5.3、Stata 15.1软... 详细信息

目的:系统评价经导管主动脉瓣置换术治疗二叶式主动脉瓣狭窄与三叶式主动脉瓣狭窄的疗效。方法:检索建库至2020年2月PubMed、Embase、Cochrane图书馆、万方数据库和中国知网的随机对照及队列研究试验,同时采用Revman 5.3、Stata 15.1软件对纳入试验进行荟萃分析。结果:纳入17项研究,共分析132333例患者。荟萃分析结果显示:BAV组与TAV组在30 d死亡率(OR=1.13,95%CI:0.89~1.44,P=0.32)、1年死亡率(OR=0.91,95%CI:0.77~1.06,P=0.22)、脑卒中(OR=1.26,95%CI:0.94~1.68,P=0.12)、瓣周漏(OR=1.17,95%CI:0.95~1.44,P=0.15)、大出血事件(OR=0.84,95%CI:0.66~1.06,P=0.13)、血管并发症(OR=0.77,95%CI:0.59~1.00,P=0.051)、冠脉阻塞(OR=1.83,95%CI:0.93~3.60,P=0.08)、术后心梗(OR=1.14,95%CI:0.63~2.06,P=0.66)、急性肾损伤(OR=1.02,95%CI:0.76~1.37,P=0.89)术后并发症方面差异无统计学差异。在手术成功率(OR=0.59,95%CI:0.39~0.94,P=0.03)上低于TAV组。中转开胸(OR=2.88,95%CI:1.61~5.18,P=0.0004)及起搏器植入(OR=1.17,95%CI:1.02~1.33,P=0.02)方面高于TAV组。结论:与TAV患者相比,BAV患者行TAVR治疗是可行的、有效的。两组的死亡率以及主要术后并发症无统计学差异。但BAV组在手术成功率上低于TAV组,中转开胸、新发起搏器植入事件高于TAV组,应该在新一代生物瓣膜中行进一步研究。

关键词：主动脉瓣狭窄二叶式主动脉瓣经导管主动脉瓣置换术荟萃分析

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剖宫产后子宫瘢痕妊娠26例临床分析

中国继续医学教育 2014年第8期6卷 52-53页

作者：张少娟抚顺市中心医院辽宁抚顺113000

目的探讨剖宫产后子宫瘢痕妊娠的临床特点。方法对医院剖宫产术后26例患者临床资料进行分析。结果药物治疗成功率90%。药物加手术治疗成功率62.5%,子宫动脉栓塞术治疗成功率为60%。子宫次全切术成功率为33.3%。结论有剖宫产史的患... 详细信息

目的探讨剖宫产后子宫瘢痕妊娠的临床特点。方法对医院剖宫产术后26例患者临床资料进行分析。结果药物治疗成功率90%。药物加手术治疗成功率62.5%,子宫动脉栓塞术治疗成功率为60%。子宫次全切术成功率为33.3%。结论有剖宫产史的患者若再次怀孕,应进行阴道彩超及血HCG检查,有助于明确诊断。

关键词：剖宫产瘢痕妊娠临床分析

一类含有界随机参数经济系统的Hopf分岔分析

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统计与决策 2017年第21期33卷 15-18页

作者：郭祥马少娟张莉莉北方民族大学数学与信息科学学院银川750021

文章应用Chebyshev正交多项式逼近法研究了一类含有界随机参数经济系统的Hopf分岔现象,随机系统首先被转化成等价的确定性系统,并得到系统发生Hopf分岔的条件,然后通过数值仿真验证了理论结果。仿真结果表明:受随机因素的影响,系统具有... 详细信息

文章应用Chebyshev正交多项式逼近法研究了一类含有界随机参数经济系统的Hopf分岔现象,随机系统首先被转化成等价的确定性系统,并得到系统发生Hopf分岔的条件,然后通过数值仿真验证了理论结果。仿真结果表明:受随机因素的影响,系统具有复杂的非线性动力学特性,并得出参数随机强度δ逐渐增大时不仅会使系统分岔参数值左移而且会抑制极限环幅值的增大。

关键词：经济系统 Hopf分岔 Chebyshev多项式

慢性心力衰竭患者入院血压水平对心源性死亡的判断价值

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临床心血管病杂志 2018年第5期34卷 489-493页

作者：林雅慧祖秀光张少娟河北医科大学第二医院心内科石家庄050000

目的:探讨慢性心力衰竭(CHF)患者入院血压水平对心源性死亡的判断价值。方法:入选2015-01-2015-12就诊于河北医科大学第二医院的CHF患者共119例,测量并记录患者入院时收缩压、舒张压及脉压,依据不同血压水平进行分组,以心源性死亡为随... 详细信息

目的:探讨慢性心力衰竭(CHF)患者入院血压水平对心源性死亡的判断价值。方法:入选2015-01-2015-12就诊于河北医科大学第二医院的CHF患者共119例,测量并记录患者入院时收缩压、舒张压及脉压,依据不同血压水平进行分组,以心源性死亡为随访终点,随访时间≥6个月,比较各组心源性死亡的发生情况。结果:119例CHF患者随访6个月后,心源性死亡22例,Kaplan-Meier生存分析结果显示,入院收缩压130mmHg者(P55 mmHg者(P<0.01)。多因素Cox风险比例模型分析显示,入院时低收缩压(RR=0.891,95%CI:0.828~0.958)和氨基末端B型钠尿肽前体升高(RR=12.921,95%CI:2.373~70.353)是CHF患者近期发生心源性死亡的主要危险因素。结论:入院时低收缩压是判断CHF患者心源性死亡的独立预测因素。

关键词：慢性心力衰竭入院血压水平心源性死亡

气候变化背景下西南山地资源型城市水安全问题与对策——以昆明东川为例

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山地学报 2016年第6期34卷 772-779页

作者：李杰邓伟张继飞李少娟黄茹张扣强中国科学院水利部成都山地灾害与环境研究所四川成都610041 云南财经大学城市与环境学院云南昆明650221 中国科学院大学北京100049

山地资源型城市地理条件复杂,近现代人类活动强烈,环境破坏严重,生态脆弱,易受气候变化影响下水资源配置与利用失衡而引发水安全问题。我国西南山区近几十年来受气候变暖影响极端干旱灾害频发,加之资源型城市地区长期存在水污染问题,区... 详细信息

山地资源型城市地理条件复杂,近现代人类活动强烈,环境破坏严重,生态脆弱,易受气候变化影响下水资源配置与利用失衡而引发水安全问题。我国西南山区近几十年来受气候变暖影响极端干旱灾害频发,加之资源型城市地区长期存在水污染问题,区内居民水安全风险较大。本研究以昆明市东川区为例,分析其近年来社会经济发展与水资源量变化趋势;并对不同海拔梯度自然村进行农村饮水、灌溉用水问卷调查;对区内主要河流进行水质采样、以分析东川现存水安全问题并提出相应对策措施。结果显示,东川区近年来水资源量有减少趋势,农业发展增速缓慢;同时区内存在水量、水质两类水安全问题;干旱期,中、高山区以山泉作为主要水源、及雨水作为主要灌溉用水的自然村常存在用水量短缺问题;大部分河流均受到不同程度重金属污染,河流水资源难以利用;河谷区人畜饮水及灌溉用水受河流水质恶化影响较重。研究提出应对措施:对中高山等水源涵养区进行生态修复;严格控制重金属排放,恢复河流水质;以及加强小水利设施建设,提高水资源利用效率。东川是典型的西南山地资源型城市,其水安全问题有一定的代表性,本研究可为上述地区水土资源耦合调控提供一定借鉴。

关键词：水安全气候变化极端干旱山地资源型城市东川

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图割综述

北方工业大学学报 2010年第3期22卷 10-15页

作者：张少娟邹建成北方工业大学图像处理与模式识别研究所北京100144

综述了图割的基本理论框架及利用图割解决问题时的主要流程和图割方法存在的难点问题.介绍了图割的发展状况及图割的应用领域,指出了其中的公开问题,并对图割未来的研究方向做出展望.

关键词：图割能量函数最大流/最小割