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71.
Dr. Xiaoyun Deng Dr. Akiko Hatori Dr. Zhen Chen Dr. Katsushi Kumata Dr. Tuo Shao Dr. Xiaofei Zhang Dr. Tomoteru Yamasaki Dr. Kuan Hu Dr. Qingzhen Yu Dr. Longle Ma Dr. Gangqiang Wang Dr. Lu Wang Prof. Dr. Yihan Shao Prof. Dr. Lee Josephson Prof. Dr. Shaofa Sun Prof. Dr. Ming-Rong Zhang Prof. Dr. Steven Liang 《ChemMedChem》2019,14(3):303-309
Muscarinic acetylcholine receptors (mAChRs) have five distinct subunits (M1–M5) and are involved in the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. Attributed to the promising clinical efficacy of xanomeline, an M1/M4-preferring agonist, in patients of schizophrenia and Alzheimer's disease, M1- or M4-selective mAChR modulators have been developed that target the topographically distinct allosteric sites. Herein we report the synthesis and preliminary evaluation of 11C-labeled positron emission tomography (PET) ligands based on a validated M4R positive allosteric modulator VU0467485 (AZ13713945) to facilitate drug discovery. [11C]VU0467485 and two other ligands were prepared in high radiochemical yields (>30 %, decay-corrected) with high radiochemical purity (>99 %) and high molar activity (>74 GBq μmol−1). In vitro autoradiography studies indicated that these three ligands possess moderate-to-high in vitro specific binding to M4R. Nevertheless, further physiochemical property optimization is necessary to overcome the challenges associated with limited brain permeability. 相似文献
72.
Dr. Aimee J. Marko Mykhaylo Dukh Dr. Nayan J. Patel Joseph R. Missert Prof. Dr. Tymish Ohulchanskyy Walter A. Tabaczynski Dr. Kei Ohkubo Prof. Dr. Shunichi Fukuzumi Prof. Dr. Rutao Yao Prof. Dr. Munawwar Sajjad Prof. Dr. Ravindra K. Pandey 《ChemMedChem》2019,14(16):1503-1513
Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1′-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the 124I isotope). The PET imaging ability and ex vivo biodistribution of [124I] 4 were compared with the well-studied methyl [3-(1241′-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [124I] 2 ) and [18F]fluorodeoxyglucose ([18F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [124I] 4 containing a fused methoxy cyclohexenone ring system showed excellent tumor contrast with time (72>48>24 h post-injection). Ex vivo biodistribution results indicate that relative to the current clinical standard [18F]FDG and [124I] 2 in 2 % ethanol formulation, [124I] 4 , at the same radioactive dose (25 μCi per mouse), showed higher tumor uptake at 24 h post-injection and longer tumor retention. In biological environments, compound 4 showed lower fluorescence and lower singlet oxygen yield than 2 , which is possibly due to higher aggregation caused by the presence of a fused cyclohexenone ring system, resulting in limited in vitro/in vivo PDT efficacy. Therefore, the chlorophyll-a analogue [124I] 4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types—brain, renal carcinomas, pancreas—in which [18F]FDG shows limitations. 相似文献
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J. Čížek O. Melikhova M. Vlček F. Lukáč M. Vlach I. Procházka W. Anwand G. Brauer A. Mücklich S. Wagner H. Uchida A. Pundt 《International Journal of Hydrogen Energy》2013
The development of the microstructure in nanocrystalline, polycrystalline and epitaxial Pd films loaded with hydrogen is investigated. Structural changes in Pd films loaded with hydrogen were characterized by positron annihilation spectroscopy combined with electron microscopy and X-ray diffraction. It was found that hydrogen charging causes plastic deformation which leads to an increase of the defect density in all Pd films studied. Moreover, the formation of buckles was observed in nanocrystalline and polycrystalline Pd films loaded above a certain critical hydrogen concentration. Buckling leads to detachment of the film from the substrate and this is accompanied with in-plane stress relaxation and plastic deformation of the film. 相似文献
75.
Bing Guan Ning Zhou Cheng-Yang Wu Songye Li Yu-An Chen Sashi Debnath Mia Hofstad Shihong Ma Ganesh V. Raj Dalin He Jer-Tsong Hsieh Yiyun Huang Guiyang Hao Xiankai Sun 《International journal of molecular sciences》2021,22(23)
Neuroendocrine prostate cancer (NEPC) is an aggressive and lethal variant of prostate cancer (PCa), and it remains a diagnostic challenge. Herein we report our findings of using synaptic vesicle glycoprotein 2 isoform A (SV2A) as a promising marker for positron emission tomography (PET) imaging of neuroendocrine differentiation (NED). The bioinformatic analyses revealed an amplified SV2A gene expression in clinical samples of NEPC versus castration-resistant PCa with adenocarcinoma characteristics (CRPC-Adeno). Importantly, significantly upregulated SV2A protein levels were found in both NEPC cell lines and tumor tissues. PET imaging studies were carried out in NEPC xenograft models with 18F-SynVesT-1. Although 18F-SynVesT-1 is not a cancer imaging agent, it showed a significant uptake level in the SV2A+ tumor (NCI-H660: 0.70 ± 0.14 %ID/g at 50–60 min p.i.). The SV2A blockade resulted in a significant reduction of tumor uptake (0.25 ± 0.03 %ID/g, p = 0.025), indicating the desired SV2A imaging specificity. Moreover, the comparative PET imaging study showed that the DU145 tumors could be clearly visualized by 18F-SynVesT-1 but not 68Ga-PSMA-11 nor 68Ga-DOTATATE, further validating the role of SV2A-targeted imaging for noninvasive assessment of NED in PCa. In conclusion, we demonstrated that SV2A, highly expressed in NEPC, can serve as a promising target for noninvasive imaging evaluation of NED. 相似文献
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用正电子湮没寿命谱和多普勒展宽方法研究高能电子(12MeV)辐照聚丙烯和聚乙烯的不同特性,发现在160kGy剂量内,正电子在聚丙烯内的短寿命成分随着电子辐照剂量的增大而变长,中间成分的强度则减弱,但当剂量为320kGy时,各湮没寿命与没有辐照的样品类似。而长寿命成分的强度不随剂量增加而变化。在电子辐照的聚乙烯薄膜中,当剂量为80kGy时,正电子中间寿命强度I2增加,长寿命成分的强度I5则有所减少。之后,随着电子辐照剂量的增加,则不再变化。正电子湮没γ射线多普勒展宽S参数随电子辐照聚乙烯的剂量变化与I5相同。正电子湮没特性的差别表明高能电子辐照这两种聚合物所引起结构上的变化是不同的,并为其宏观特性(如力学性质变化)的改变提供了微观依据。 相似文献
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80.
Grady Cheryl L.; Bernstein Lori J.; Beig Sania; Siegenthaler Amy L. 《Canadian Metallurgical Quarterly》2002,17(1):7
Age-related differences in brain activity mediating face recognition were examined using positron emission tomography. Participants encoded faces using a pleasant-unpleasant judgement, a right-left orientation task, and intentional learning. Scans also were obtained during recognition. Both young and old groups showed significant effects of encoding task on recognition accuracy, but older adults showed reduced accuracy overall. Increased brain activity in older adults was similar to that seen in young adults during conditions associated with deeper processing, but was reduced during the shallow encoding and recognition conditions. Differential correlations of brain activity and behavior were found that suggest older adults use unique neural systems to facilitate face memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献