CN106344934A - 一种荧光化合物在Aβ斑块显像制剂中的应用 - Google Patents
一种荧光化合物在Aβ斑块显像制剂中的应用 Download PDFInfo
- Publication number
- CN106344934A CN106344934A CN201610808146.8A CN201610808146A CN106344934A CN 106344934 A CN106344934 A CN 106344934A CN 201610808146 A CN201610808146 A CN 201610808146A CN 106344934 A CN106344934 A CN 106344934A
- Authority
- CN
- China
- Prior art keywords
- application
- beta plaque
- beta
- alpha
- fluorescent chemicalses
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000012216 imaging agent Substances 0.000 title claims abstract description 10
- 239000000126 substance Substances 0.000 title abstract description 9
- 238000003745 diagnosis Methods 0.000 claims abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 4
- 230000006933 amyloid-beta aggregation Effects 0.000 claims description 2
- 230000004807 localization Effects 0.000 claims description 2
- 230000008901 benefit Effects 0.000 abstract description 4
- 238000000799 fluorescence microscopy Methods 0.000 abstract description 4
- 230000035515 penetration Effects 0.000 abstract description 3
- 230000005855 radiation Effects 0.000 abstract description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 abstract description 2
- 230000007704 transition Effects 0.000 abstract description 2
- 206010035148 Plague Diseases 0.000 abstract 1
- 241000607479 Yersinia pestis Species 0.000 abstract 1
- 125000006575 electron-withdrawing group Chemical group 0.000 abstract 1
- 239000000523 sample Substances 0.000 description 23
- 210000004556 brain Anatomy 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 241000699660 Mus musculus Species 0.000 description 10
- 238000003384 imaging method Methods 0.000 description 10
- 238000011830 transgenic mouse model Methods 0.000 description 10
- 238000001514 detection method Methods 0.000 description 6
- 230000002776 aggregation Effects 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000006269 (delayed) early viral mRNA transcription Effects 0.000 description 1
- 208000018282 ACys amyloidosis Diseases 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 206010002025 Amyloidosis senile Diseases 0.000 description 1
- PJQMYUHLAJJKJK-AATRIKPKSA-N CC(C)(CC(/C=C/c(cc1)ccc1N(C)C)=C1)CC1=C(C#N)C#N Chemical compound CC(C)(CC(/C=C/c(cc1)ccc1N(C)C)=C1)CC1=C(C#N)C#N PJQMYUHLAJJKJK-AATRIKPKSA-N 0.000 description 1
- 206010007509 Cardiac amyloidosis Diseases 0.000 description 1
- 208000007487 Familial Cerebral Amyloid Angiopathy Diseases 0.000 description 1
- 208000032849 Hereditary cerebral hemorrhage with amyloidosis Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 241000406668 Loxodonta cyclotis Species 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 238000000695 excitation spectrum Methods 0.000 description 1
- 238000012757 fluorescence staining Methods 0.000 description 1
- 238000012632 fluorescent imaging Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000006919 peptide aggregation Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本发明属于特异性分子识别诊断试剂领域,公开了一种荧光化合物在Aβ斑块显像制剂中的应用。所述荧光化合物的结构如式(I)所示。本发明的荧光化合物,其结构中的给电子基团和吸电子基团形成了推‑拉电子作用的共轭结构,并通过碳碳双键增加跃迁的共轭体系,使化合物分子产生的荧光向近红外区移动,同时该化合物分子对Aβ斑块具有亲和力,能够成功用于Aβ斑块的近红外荧光显像,具有安全无放射性、成本低廉、背景荧光干扰较低、在生物组织中穿透力强等优点。
Description
技术领域
本发明属于特异性分子识别诊断试剂领域,具体涉及一种荧光化合物在Aβ斑块显像制剂中的应用。
背景技术
阿尔茨海默症(Alzheimer’s disease,AD)是一种神经退行性疾病。调查数据显示,目前全球范围内有超过4000万AD病人。而中国已提前进入老龄化社会,调查显示我国已有超过800万AD患者,数量居世界之首,且患病人数以每年30万以上的速度递增。AD不但严重影响老年人健康的疾病,并给社会和家庭带来沉重的负担。目前,临床上可用于治疗AD的药物不能延缓、终止或者逆转AD病情的发展,只能部分改善临床症状。而且,由于AD病因复杂,确切的发病机理目前尚不清楚,临床上主要通过评价患者的认知能力损伤来诊断,确诊患者多已进入病程的中晚期而延误了治疗。缺乏有效的检测手段,已成为AD早起诊断和治疗的重大障碍。
在AD患者脑中,β-淀粉样蛋白(Amyloid,Aβ)在脑中沉积是AD最为显著的病理性标志之一。Aβ斑块在AD发病前的数十年已开始出现,是AD最早的神经组织退化标志和重要病理学特征。近年来,Aβ斑块形成的预防和逆转成为治疗AD的目标之一,抑制Aβ斑块在脑内产生和蓄积的药物和疗法得到了广泛研究。
除了AD外,Aβ斑块也存在于其他疾病中,例如脑淀粉样血管病、淀粉样心肌病、淀粉样多发性神经病、系统性老年淀粉样变和伴有淀粉样变的遗传性脑出血等。因此,研发具有特异性结合Aβ斑块的Aβ分子探针引人关注。利用Aβ分子探针和分子成像技术进行Aβ斑块的显像,可实现无创的、实时的Aβ斑块的体内示踪和检测,进而为AD等疾病患者进行早期诊断、疗效检测以及治疗药物的研究等提供极大便利。
过去的数年间,已有较多放射性Aβ分子探针进入临床试验阶段,并有相关PET成像试剂上市,但是放射性显像方法的应用也受一些因素限制,比如放射性显像剂所发出的射线对人体具有一定的辐射损伤、需要医疗机构配套有生产放射性核素的回旋加速器、放射性显像剂需专业技术人员标记配制等。相比较之下,光学成像具有安全无放射性、数据采集时间短以及成本低廉等诸多优势,近年在医学诊断等中的应用受到广泛重视。尤其是近红外荧光成像技术,因其背景荧光干扰较低,在生物组织中穿透力强,因此,研发对Aβ斑块具有亲和力的近红外荧光显像剂(分子探针),将具有重要的科学意义和实际价值。
发明内容
为了解决以上现有技术的缺点和不足之处,本发明的目的在于提供一种荧光化合物在Aβ斑块显像制剂中的应用。
本发明目的通过以下技术方案实现:
一种荧光化合物在Aβ斑块显像制剂中的应用,所述荧光化合物的结构如式(I)所示:
上述荧光化合物在Aβ斑块显像诊断组合物中的应用,所述组合物包括式(I)所示的化合物与药学上可接受的载体。所述“药学上可接受的载体”包括各种赋形剂和稀释剂。本发明所述的在组合物中药学上可接受的载体可包括液体,如水、生理盐水、甘油和乙醇。
上述荧光化合物在Aβ沉积相关疾病的诊断试剂和治疗药物中的应用。
所述的Aβ沉积相关疾病是指阿尔茨海默症或脑淀粉样血管病。
本发明提供Aβ斑块的显像方法。在本显像方法的第一步中,将可检测量的式(I)所示的化合物引入组织或患者中。化合物通常是诊断组合物的部分并且通过本领域技术人员公知的方法给药至组织或患者。如以可检测量的式(I)所示的化合物引入患者并且在足以使化合物与Aβ斑块结合的时间之后,非创伤性地检测化合物。或将式(I)所示的化合物引入患者,经足量的时间以使化合物与Aβ斑块结合,自患者取组织样品,并脱离患者检测组织中的化合物。或自患者取组织样品并且将式(I)所示的化合物引入该组织样品。在足以使该化合物结合至Aβ斑块的时间之后,检测化合物。
可以通过整体的或局部的给药途径将式(I)所示的化合物给药至患者。例如,可以将化合物给药至患者以使其递送至全身。可选地,可以将化合物给药至关注的特定的器官或者组织。例如,为了诊断或追踪患者的AD的进程,需要定位和定量脑内的淀粉样斑块。
术语“患者”是指人类和其他动物。本领域技术人员也熟知如何确定足以使化合物与Aβ斑块结合的时间。通过将可检测量的式(I)所示的化合物引入患者,然后在给药后的各时间处检测化合物,可以容易地测定所需的时间。
术语“结合”是指化合物和Aβ斑块之间的化学相互作用。结合的实例包括共价键、离子键、亲水-亲水相互作用、疏水-疏水相互作用和络合物。
本发明所述的显像手段为光学显像。
相对于现有技术,本发明的荧光化合物用于Aβ斑块显像具有如下优点及有益效果:
本发明的荧光化合物,其结构中的给电子基团和吸电子基团形成了推-拉电子作用的共轭结构,并通过碳碳双键增加跃迁的共轭体系,使化合物分子产生的荧光向近红外区移动,同时该化合物分子对Aβ斑块具有亲和力,能够成功用于Aβ斑块的近红外荧光显像,具有安全无放射性、成本低廉、背景荧光干扰较低、在生物组织中穿透力强等优点。
附图说明
图1是实施例1所得荧光化合物(I)探针与Aβ1-42聚集体混合前后的荧光发射光谱图;
图2是实施例2所得荧光化合物(I)探针由尾静脉注入AD转基因小鼠和正常小鼠后60min内不同时间点脑部活体成像图;
图3是实施例2所得荧光化合物(I)探针由尾静脉注入AD转基因小鼠和正常小鼠后各时间点脑的荧光信号图;
图4是实施例3所得荧光化合物(I)探针由尾静脉注入AD转基因小鼠30分钟后,脑切片荧光成像图。
具体实施方式
下面结合实施例及附图对本发明作进一步详细的描述,但本发明的实施方式不限于此。
实施例1
荧光化合物(I)探针与Aβ1-42聚集体的体外结合实验:
实验方法:取荧光化合物(I)(按照文献方法制备:Chemistry of Materials,9(6),1437-1442;1997)溶于二甲亚砜中,配制成10mM储备液,用PBS溶液稀释成1μM的待测液(探针(I))。先测得探针(I)的激发和发射光谱性质。选用Aβ1-42蛋白在37℃水浴中培育Aβ聚集体,用于模拟人脑内的Aβ蛋白聚集体。将探针(I)与Aβ1-42聚集体(5μM)混合,应用荧光分光光度计进行荧光检测。
本实施例中探针(I)与Aβ1-42聚集体混合前后的荧光光谱图见图1。由图1可以看出,本发明的荧光化合物(I)在PBS中的最大发射波长为680nm,达到了近红外区。荧光化合物(I)与Aβ聚集体结合后,发射波长出现蓝移,最大发射波长为635nm左右。荧光化合物(I)与Aβ1-42聚集体混合后的荧光强度大幅增强,为化合物自身荧光强度的12倍。
实施例2
荧光化合物(I)探针应用于AD转基因小鼠活体成像:
实验步骤:将荧光化合物(I)溶液探针(4mg/kg,10%吐温80、20%DMSO、70%PBS)由尾静脉注射入AD转基因小鼠(Tg,APP/PS1双转,10月龄)和正常小鼠(WT,C57BL6,10月龄)体内,在异氟烷的持续麻醉下分别在10min、30min、60min进行小鼠动物成像图像采集(Caliper Life Science,IVIS LuminaXR,激发波长取500nm,发射波长取635nm和680nm),分析结果。采用Living Imaging Software进行成像结果分析。
本实施例的成像实验结果如图2和图3所示。结果显示,荧光化合物(I)可以透过血脑屏障,脑部的荧光信号在10分钟左右达到峰值。10分钟之后,AD转基因小鼠的脑部荧光信号强度要强于正常小鼠。荧光化合物(I)在AD转基因小鼠体内的清除速率(10min/60min=1.76)明显要慢于正常小鼠(10min/60min=2.78),表明探针与小鼠脑内的Aβ斑块结合后滞留在小鼠脑部,使AD小鼠脑部的荧光信号明显高于正常小鼠,适用于活体的荧光成像。
实施例3
荧光化合物(I)探针应用于AD转基因小鼠体内荧光染色
实验步骤:将实施例2中活体显像所用的AD转基因小鼠(APP/PS1双转)饲养15天,让探针在其体内彻底代谢。将荧光化合物(I)溶液探针(4mg/kg,10%吐温80、20%DMSO、70%PBS)由尾静脉注射入AD转基因小鼠(11月龄)体内,30分钟后断颈处死,迅速取出脑组织,用20g/L蔗糖与OCT混合包埋剂(1:1)包埋后置于-20℃冷冻20-30分钟,然后进行切片(10μm)。待切片在室温干燥后,置于荧光显微镜下观察、拍照,结果如图4A所示。相同的切片用硫磺素S进行染色(0.3%,水:乙醇=1:1),同样用荧光显微镜观察、拍照,结果如图4B所示。由图4A和4B结果表明,荧光化合物(I)能与小鼠脑内的Aβ斑块进行清晰的染色;用硫磺素S进行的对比染色(图4B)可以很好的与化合物染色的斑块重合,进一步说明我们的探针在AD小鼠脑内标记的是Aβ斑块。
上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其它的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。
Claims (4)
1.一种荧光化合物在Aβ斑块显像制剂中的应用,其特征在于所述荧光化合物的结构如式(I)所示:
2.根据权利要求1所述的一种荧光化合物在Aβ斑块显像制剂中的应用,其特征在于:所述荧光化合物用于制备Aβ斑块显像诊断组合物,所述组合物包括式(I)所示的化合物与药学上可接受的载体。
3.根据权利要求1所述的一种荧光化合物在Aβ斑块显像制剂中的应用,其特征在于:所述荧光化合物用于制备Aβ沉积相关疾病的诊断试剂和治疗药物。
4.根据权利要求3所述的一种荧光化合物在Aβ斑块显像制剂中的应用,其特征在于:所述的Aβ沉积相关疾病是指阿尔茨海默症或脑淀粉样血管病。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610808146.8A CN106344934A (zh) | 2016-09-07 | 2016-09-07 | 一种荧光化合物在Aβ斑块显像制剂中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610808146.8A CN106344934A (zh) | 2016-09-07 | 2016-09-07 | 一种荧光化合物在Aβ斑块显像制剂中的应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106344934A true CN106344934A (zh) | 2017-01-25 |
Family
ID=57859310
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610808146.8A Pending CN106344934A (zh) | 2016-09-07 | 2016-09-07 | 一种荧光化合物在Aβ斑块显像制剂中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106344934A (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108061725A (zh) * | 2017-02-16 | 2018-05-22 | 昆明医科大学 | 1,8-萘啶基荧光分子探针在氯胺酮娱乐性滥用神经机制研究及成瘾程度诊断中的应用 |
CN115340511A (zh) * | 2021-05-13 | 2022-11-15 | 中国科学院大连化学物理研究所 | 荧光化合物、其制备方法及作为荧光探针的应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1283665A (zh) * | 2000-08-31 | 2001-02-14 | 山东大学 | 一种用于电致发光器件的红色荧光材料及制备方法 |
CN104178132A (zh) * | 2014-07-30 | 2014-12-03 | 四川大学 | 一种荧光化合物及其在医药上的用途 |
-
2016
- 2016-09-07 CN CN201610808146.8A patent/CN106344934A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1283665A (zh) * | 2000-08-31 | 2001-02-14 | 山东大学 | 一种用于电致发光器件的红色荧光材料及制备方法 |
CN104178132A (zh) * | 2014-07-30 | 2014-12-03 | 四川大学 | 一种荧光化合物及其在医药上的用途 |
Non-Patent Citations (1)
Title |
---|
XU ZHANG ET AL.: "Synthesis and fluorescence of dicyanoisophorone derivatives", 《DYES AND PIGMENTS》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108061725A (zh) * | 2017-02-16 | 2018-05-22 | 昆明医科大学 | 1,8-萘啶基荧光分子探针在氯胺酮娱乐性滥用神经机制研究及成瘾程度诊断中的应用 |
CN115340511A (zh) * | 2021-05-13 | 2022-11-15 | 中国科学院大连化学物理研究所 | 荧光化合物、其制备方法及作为荧光探针的应用 |
CN115340511B (zh) * | 2021-05-13 | 2023-10-31 | 中国科学院大连化学物理研究所 | 荧光化合物、其制备方法及作为荧光探针的应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Hu et al. | First-in-human liver-tumour surgery guided by multispectral fluorescence imaging in the visible and near-infrared-I/II windows | |
Martirosyan et al. | Use of in vivo near-infrared laser confocal endomicroscopy with indocyanine green to detect the boundary of infiltrative tumor | |
Tummers et al. | Intraoperative guidance in parathyroid surgery using near-infrared fluorescence imaging and low-dose Methylene Blue | |
Liu et al. | Highly specific noninvasive photoacoustic and positron emission tomography of brain plaque with functionalized croconium dye labeled by a radiotracer | |
JP6751715B2 (ja) | 神経結合選択性が増強された環状ペプチド、当該環状ペプチドと結合したナノ粒子、およびリアルタイムin vivo神経組織撮像ための当該環状ペプチドの使用 | |
Ashitate et al. | Real-time simultaneous near-infrared fluorescence imaging of bile duct and arterial anatomy | |
Fang et al. | Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging with indocyanine green | |
Beziere et al. | Optoacoustic imaging and staging of inflammation in a murine model of arthritis | |
CN107057398B (zh) | 一种七甲川菁荧光染料及其肿瘤精准诊断和治疗的应用 | |
US20080154102A1 (en) | Intraoperative imaging methods | |
WO2011077751A1 (ja) | 中枢神経系組織標識用組成物、中枢神経系組織の標識方法、及び中枢神経系組織標識用組成物を用いたスクリーニング方法 | |
Wang et al. | Applications of fluorescence lifetime imaging in clinical medicine | |
Folaron et al. | Elucidating the kinetics of sodium fluorescein for fluorescence-guided surgery of glioma | |
Akshulakov et al. | Current trends for improving safety of stereotactic brain biopsies: advanced optical methods for vessel avoidance and tumor detection | |
van Willigen et al. | Multispectral fluorescence guided surgery; a feasibility study in a phantom using a clinical-grade laparoscopic camera system | |
Zhang et al. | Imaging of rat cerebral ischemia-reperfusion injury using99mTc-labeled duramycin | |
CN107325809B (zh) | 一种与Aβ斑块具有亲和力的荧光化合物及制备与应用 | |
Cho et al. | Evaluation of diagnostic accuracy following the coadministration of delta-aminolevulinic acid and second window indocyanine green in rodent and human glioblastomas | |
WO2008043101A2 (en) | Intraoperative imaging of hepatobiliary structures | |
CN106344934A (zh) | 一种荧光化合物在Aβ斑块显像制剂中的应用 | |
CN108144072B (zh) | 用于诊断凝集素受体高表达肿瘤的放射性药物 | |
Dip et al. | Nerve spectroscopy: understanding peripheral nerve autofluorescence through photodynamics | |
Yang et al. | Characterization of cryoinjury-induced infarction with manganese-and gadolinium-enhanced MRI and optical spectroscopy in pig hearts | |
Gao et al. | Mechanism of dynamic near-infrared fluorescence cholangiography of extrahepatic bile ducts and applications in detecting bile duct injuries using indocyanine green in animal models | |
CN107847616A (zh) | 针对癌症的早期骨转移的诊断显像剂 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170125 |