American Chemical Society (ACS)Acta Medica Okayama2574-09622025Enhanced Charge-Transfer Kinetics Enabled by ZrO2–Based Dielectric Layers in Lithium-Ion BatteriesENTakashiTeranishiGraduate School of Natural Science and Technology, Okayama UniversityYusukeHigakiGraduate School of Natural Science and Technology, Okayama UniversityTomonoriImamuraGraduate School of Natural Science and Technology, Okayama UniversityMotokiHoribeDepartment of Advanced Ceramics, Nagoya Institute of TechnologyShinyaKondoDepartment of Energy Engineering, Nagoya UniversityChinatsuSasaokaR&D Laboratory, Nippon Denko Co., Ltd.HikaruHirabaruR&D Laboratory, Nippon Denko Co., Ltd.ShingoKatayamaR&D Laboratory, Nippon Denko Co., Ltd.MasanobuNakayamaDepartment of Advanced Ceramics, Nagoya Institute of TechnologyAkiraKishimotoGraduate School of Natural Science and Technology, Okayama UniversityThe development of high-rate capability lithium-ion batteries (LIBs) requires suppression of charge-transfer resistance (RCT) at electrode–electrolyte interfaces. Here, zirconia-based dielectric oxides (MZ; M = Y, Gd, Sm, Er, etc.) were introduced onto LiCoO2 (LCO) surfaces as electronically and ionically insulating modifiers to accelerate interfacial ion transport. Electrochemical impedance spectroscopy showed that Y2O3 modified ZrO2 (YZ) decoration reduced RCT from 75.8 ƒ¶ in reference LCO to 38.3 ƒ¶, accompanied by a 2.3-fold improvement in capacity retention at 20C. Density functional theory molecular dynamics (DFT–MD) simulations showed that solvated Li ions coordinate with surface oxygen atoms in discharging, and that adsorption energies are governed by local charge distributions determined by stabilizing cations. Optimal adsorption activity, and thus the lowest RCT, occurred when the surface charge corrugation was balanced. These findings provide design principles for dielectric interface engineering to enhance rate capability of LIBs.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama0968-08962812020Development and characterization of a 68Ga-labeled A20FMDV2 peptide probe for the PET imaging of ƒ¿vƒÀ6 integrin-positive pancreatic ductal adenocarcinoma115189ENTakashiUiGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasashiUedaGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYusukeHigakiGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversitShinichiroKaminoGraduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKoheiSanoGraduate School of Pharmaceutical Sciences, Kyoto UniversityHiroyukiKimuraGraduate School of Pharmaceutical Sciences, Kyoto UniversityHideoSajiGraduate School of Pharmaceutical Sciences, Kyoto UniversityShuichiEnomotoRIKEN Center for Life Science TechnologiesPancreatic ductal adenocarcinoma (PDAC) is known to be one of the most lethal cancers. Since the majority of patients are diagnosed at an advanced stage, development of a detection method for PDAC at an earlier stage of disease progression is strongly desirable. Integrin ƒ¿VƒÀ6 is a promising target for early PDAC detection because its expression increases during precancerous changes. The present study aimed to develop an imaging probe for positron emission tomography (PET) which targets ƒ¿VƒÀ6 integrin-positive PDAC. We selected A20FMDV2 peptide, which binds specifically to ƒ¿vƒÀ6 integrin, as a probe scaffold, and 68Ga as a radioisotope. A20FMDV2 peptide has not been previously labeled with 68Ga. A cysteine residue was introduced to the N-terminus of the probe at a site-specific conjugation of maleimide-NOTA (mal-NOTA) chelate. Different numbers of glycine residues were also introduced between cysteine and the A20FMDV2 sequence as a spacer in order to reduce the steric hindrance of the mal-NOTA on the binding probe to ƒ¿VƒÀ6 integrin. In vitro, the competitive binding assay revealed that probes containing a 6-glycine linker ([natGa]CG6 and [natGa]Ac-CG6) showed high affinity to ƒ¿VƒÀ6 integrin. Both probes could be labeled by 67/68Ga with high radiochemical yield (>50%) and purity (>98%). On biodistribution analysis, [67Ga]Ac-CG6 showed higher tumor accumulation, faster blood clearance, and lower accumulation in the surrounding organs of pancreas than did [67Ga]CG6. The ƒ¿VƒÀ6 integrin-positive xenografts were clearly visualized by PET imaging with [68Ga]Ac-CG6. The intratumoral distribution of [68Ga]Ac-CG6 coincided with the ƒ¿VƒÀ6 integrin-positive regions detected by immunohistochemistry. Thus, [68Ga]Ac-CG6 is a useful peptide probe for the imaging of ƒ¿VƒÀ6 integrin in PDAC.No potential conflict of interest relevant to this article was reported.Elsevier ScienceActa Medica Okayama 0969-80514362016Noninvasive evaluation of nicotinic acetylcholine receptor availability in mouse brain using single-photon emission computed tomography with [(123)I]5IA.372378ENYukiMatsuuraDepartment of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasashiUedaDepartment of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYusukeHigakiDepartment of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKeikoWatanabeDepartment of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityShogoHabaraDepartment of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityShinichiroKaminoDepartment of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHideoSajiDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto UniversityShuichiEnomotoDepartment of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityINTRODUCTION:<br/>
Nicotinic acetylcholine receptors (nAChRs) are of great interest because they are implicated in higher brain functions. Nuclear medical imaging is one of the useful techniques for noninvasive evaluation of physiological and pathological function in living subjects. Recent progress in nuclear medical imaging modalities enables the clear visualization of the organs of small rodents. Thus, translational research using nuclear medical imaging in transgenic mice has become possible and helps to elucidate human disease pathology. However, imaging of ƒ¿4ƒÀ2 nAChRs in the mouse brain has not yet been performed. The purpose of this study was to assess the feasibility of single-photon emission computed tomography (SPECT) with 5-[(123)I]iodo-3-[2(S)-azetidinylmethoxy]pyridine ([(123)I]5IA) for evaluating ƒ¿4ƒÀ2 nAChR availability in the mouse brain.<br/>
METHODS:<br/>
A 60-min dynamic SPECT imaging session of ƒ¿4ƒÀ2 nAChRs in the mouse brain was performed. The regional distribution of radioactivity in the SPECT images was compared to the density of ƒ¿4ƒÀ2 nAChRs measured in an identical mouse. Alteration of nAChR density in the brains of Tg2576 mice was also evaluated.<br/>
RESULTS:<br/>
The mouse brain was clearly visualized by [(123)I]5IA-SPECT and probe accumulation was significantly inhibited by pretreatment with (-)-nicotine. The regional distribution of radioactivity in SPECT images showed a significant positive correlation with ƒ¿4ƒÀ2 nAChR density measured in an identical mouse brain. Moreover, [(123)I]5IA-SPECT was able to detect the up-regulation of ƒ¿4ƒÀ2 nAChRs in the brains of Tg2576 transgenic mice.<br/>
CONCLUSIONS:<br/>
[(123)I]5IA-SPECT imaging would be a promising tool for evaluating ƒ¿4ƒÀ2 nAChR availability in the mouse brain and may be useful in translational research focused on nAChR-related diseases.No potential conflict of interest relevant to this article was reported.SpringerActa Medica Okayama1536-16322132018Evaluation of the Relationship Between Cognitive Impairment, Glycometabolism, and Nicotinic Acetylcholine Receptor Deficits in a Mouse Model of Alzheimer's Disease519528ENYukiMatsuuraDepartment of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasashiUedaDepartment of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYusukeHigakiDepartment of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKoheiSanoDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto UniversityHideoSajiDepartment of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto UniversityShuichiEnomotoDepartment of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityPURPOSE:<br/>
In patients with Alzheimer's disease (AD), the loss of cerebral nicotinic acetylcholine receptors (nAChRs) that are implicated in higher brain functions has been reported. However, it is unclear if nAChR deficits occur in association with cognitive impairments. The purpose of this study was to assess the relationship between nAChR deficits and cognitive impairments in a mouse model of AD (APP/PS2 mice).<br/>
PROCEDURES:<br/>
The cognitive abilities of APP/PS2 and wild-type mice (aged 2-16 months) were evaluated using the novel object recognition test. Double-tracer autoradiography analyses with 5-[125I]iodo-A-85380 ([125I]5IA: ƒ¿4ƒÀ2 nAChR imaging probe) and 2-deoxy-2-[18F]fluoro-D-glucose were performed in both mice of different ages. [123I]5IA-single-photon emission tomography (SPECT) imaging was also performed in both mice at 12 months of age. Furthermore, each age cohort was investigated for changes in cognitive ability and expression levels of ƒ¿7 nAChRs and N-methyl-D-aspartate receptors (NMDARs).
<br/>RESULTS:<br/>
No significant difference was found between the APP/PS2 and wild-type mice at 2-6 months of age in terms of novel object recognition memory; subsequently, however, APP/PS2 mice showed a clear cognitive deficit at 12 months of age. [125I]5IA accumulation decreased in the brains of 12-month-old APP/PS2 mice, i.e., at the age at which cognitive impairments were first observed; this result was supported by a reduction in the protein levels of ƒ¿4 nAChRs using Western blotting. nAChR deficits could be noninvasively detected by [123I]5IA-SPECT in vivo. In contrast, no significant changes in glycometabolism, expression levels of ƒ¿7 nAChRs, or NMDARs were associated with cognitive impairments in APP/PS2 mice.<br/>
CONCLUSION:<br/>
A decrease in cerebral ƒ¿4ƒÀ2 nAChR density could act as a biomarker reflecting cognitive impairments associated with AD pathology.No potential conflict of interest relevant to this article was reported.