start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=2 article-no= start-page=370 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=20240205 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Morphometric Analysis of the Eye by Magnetic Resonance Imaging in MGST2-Gene-Deficient Mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Strabismus, a neuro-ophthalmological condition characterized by misalignment of the eyes, is a common ophthalmic disorder affecting both children and adults. In our previous study, we identified the microsomal glutathione S-transferase 2 (MGST2) gene as one of the potential candidates for comitant strabismus susceptibility in a Japanese population. The MGST2 gene belongs to the membrane-associated protein involved in the generation of pro-inflammatory mediators, and it is also found in the protection against oxidative stress by decreasing the reactivity of oxidized lipids. To look for the roles of the MGST2 gene in the development, eye alignment, and overall morphology of the eye as the possible background of strabismus, MGST2 gene knockout (KO) mice were generated by CRISPR/Cas9-mediated gene editing with guide RNAs targeting the MGST2 exon 2. The ocular morphology of the KO mice was analyzed through high-resolution images obtained by a magnetic resonance imaging (MRI) machine for small animals. The morphometric analyses showed that the height, width, and volume of the eyeballs in MGST2 KO homozygous mice were significantly greater than those of wild-type mice, indicating that the eyes of MGST2 KO homozygous mice were significantly enlarged. There were no significant differences in the axis length and axis angle. These morphological changes may potentially contribute to the development of a subgroup of strabismus. en-copyright= kn-copyright= en-aut-name=Chaomulige en-aut-sei=Chaomulige en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsuoToshihiko en-aut-sei=Matsuo en-aut-mei=Toshihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SugimotoKohei en-aut-sei=Sugimoto en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiyajiMary en-aut-sei=Miyaji en-aut-mei=Mary kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HosoyaOsamu en-aut-sei=Hosoya en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UedaMasashi en-aut-sei=Ueda en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobayashiRyosuke en-aut-sei=Kobayashi en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HoriiTakuro en-aut-sei=Horii en-aut-mei=Takuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HatadaIzuho en-aut-sei=Hatada en-aut-mei=Izuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil= Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Department of Medical Neurobiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Medical Neurobiology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Biofunctional Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=8 en-affil=Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= affil-num=9 en-affil=Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University kn-affil= en-keyword=comitant strabismus kn-keyword=comitant strabismus en-keyword=MGST2 gene kn-keyword=MGST2 gene en-keyword=mouse models kn-keyword=mouse models en-keyword=genetics kn-keyword=genetics en-keyword=CRISPR/Cas9 kn-keyword=CRISPR/Cas9 en-keyword=PCR kn-keyword=PCR en-keyword=MRI kn-keyword=MRI en-keyword=eye morphology kn-keyword=eye morphology en-keyword=neuro-ophthalmology kn-keyword=neuro-ophthalmology END start-ver=1.4 cd-journal=joma no-vol=34 cd-vols= no-issue= article-no= start-page=575 end-page=582 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Improvement of biodistribution profile of a radiogallium-labeled, αvβ6 integrin-targeting peptide probe by incorporation of negatively charged amino acids en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Since αvβ6 integrin has been reported as a promising target for PDAC diagnosis, we previously developed H-Cys(mal-NOTA-67Ga)-(Gly)6-A20FMDV2-NH2 ([67Ga]CG6) as an αvβ6 integrin-targeting probe. Although [67Ga]CG6 specifically binds to αvβ6 integrin-positive xenografts, the uptake of [67Ga]CG6 in the organs surrounding the pancreas, such as the liver and spleen, was comparable to that in the αvβ6 integrin-positive xenografts. We hypothesized that the undesirable accumulation of [67Ga]CG6 in those organs was caused by the positive charges of [67Ga]CG6 (+ 3). In this study, we aimed to decrease [67Ga]CG6 uptake in the liver and spleen by reducing the electric charges of the probe.
Methods
We synthesized H-Cys(mal-NOTA-67Ga)-(Asp)6-A20FMDV2-NH2 ([67Ga]CD6) and evaluated its affinity to αvβ6 integrin via in vitro competitive binding assay. Isoelectric points of the probes were determined by electrophoresis. Biodistribution study, autoradiography, and immunostaining for β6 integrin were conducted using αvβ6 integrin-positive and negative tumor-bearing mice.
Results
In vitro competitive binding assay showed that the alteration of the linker had a negligible impact on the affinity of [67Ga]CG6 to αvβ6 integrin. The results of electrophoresis revealed that [67Ga]CG6 was positively charged whereas [67Ga]CD6 was negatively charged. In the biodistribution study, the uptake of [67Ga]CD6 in the αvβ6 integrin-positive xenografts was significantly higher than that in the αvβ6 integrin-negative ones at 60 and 120 min. The uptake of [67Ga]CD6 in the liver and spleen was more than two-fold lower than that of [67Ga]CG6 at both time points. In the immunohistochemistry study, the radioactivity accumulated areas in the autoradiogram of the αvβ6 integrin-positive xenograft roughly coincided with β6 integrin-expressing areas.
Conclusion
We have successfully reduced the nonspecific uptake in the liver and spleen by altering the linker amino acid from G6 to D6. [67Ga]CD6 overcame the drawbacks of [67Ga]CG6 in its biodistribution. en-copyright= kn-copyright= en-aut-name=NakamuraShunsuke en-aut-sei=Nakamura en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsunoAya en-aut-sei=Matsuno en-aut-mei=Aya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UedaMasashi en-aut-sei=Ueda en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=αvβ6 integrin kn-keyword=αvβ6 integrin en-keyword=Pancreatic ductal adenocarcinoma (PDAC) kn-keyword=Pancreatic ductal adenocarcinoma (PDAC) en-keyword=A20FMDV2 kn-keyword=A20FMDV2 en-keyword=Aspartic acids kn-keyword=Aspartic acids en-keyword=Electric charge kn-keyword=Electric charge END start-ver=1.4 cd-journal=joma no-vol=28 cd-vols= no-issue=1 article-no= start-page=115189 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Development and characterization of a 68Ga-labeled A20FMDV2 peptide probe for the PET imaging of αvβ6 integrin-positive pancreatic ductal adenocarcinoma en-subtitle= kn-subtitle= en-abstract= kn-abstract=Pancreatic 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 αVβ6 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 αVβ6 integrin-positive PDAC. We selected A20FMDV2 peptide, which binds specifically to αvβ6 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 αVβ6 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 αVβ6 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 αVβ6 integrin-positive xenografts were clearly visualized by PET imaging with [68Ga]Ac-CG6. The intratumoral distribution of [68Ga]Ac-CG6 coincided with the αVβ6 integrin-positive regions detected by immunohistochemistry. Thus, [68Ga]Ac-CG6 is a useful peptide probe for the imaging of αVβ6 integrin in PDAC. en-copyright= kn-copyright= en-aut-name=UiTakashi en-aut-sei=Ui en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaMasashi en-aut-sei=Ueda en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HigakiYusuke en-aut-sei=Higaki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KaminoShinichiro en-aut-sei=Kamino en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SanoKohei en-aut-sei=Sano en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KimuraHiroyuki en-aut-sei=Kimura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SajiHideo en-aut-sei=Saji en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EnomotoShuichi en-aut-sei=Enomoto en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama Universit kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= affil-num=6 en-affil=Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= affil-num=7 en-affil=Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= affil-num=8 en-affil=RIKEN Center for Life Science Technologies kn-affil= en-keyword=αvβ6 integrin kn-keyword=αvβ6 integrin en-keyword=Pancreatic ductal adenocarcinoma kn-keyword=Pancreatic ductal adenocarcinoma en-keyword=Gallium-68 kn-keyword=Gallium-68 en-keyword=A20FMDV2 peptide kn-keyword=A20FMDV2 peptide en-keyword=Positron emission tomography kn-keyword=Positron emission tomography END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=6 article-no= start-page=372 end-page=378 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201606 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Noninvasive evaluation of nicotinic acetylcholine receptor availability in mouse brain using single-photon emission computed tomography with [(123)I]5IA. en-subtitle= kn-subtitle= en-abstract= kn-abstract=INTRODUCTION:
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 α4β2 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 α4β2 nAChR availability in the mouse brain.
METHODS:
A 60-min dynamic SPECT imaging session of α4β2 nAChRs in the mouse brain was performed. The regional distribution of radioactivity in the SPECT images was compared to the density of α4β2 nAChRs measured in an identical mouse. Alteration of nAChR density in the brains of Tg2576 mice was also evaluated.
RESULTS:
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 α4β2 nAChR density measured in an identical mouse brain. Moreover, [(123)I]5IA-SPECT was able to detect the up-regulation of α4β2 nAChRs in the brains of Tg2576 transgenic mice.
CONCLUSIONS:
[(123)I]5IA-SPECT imaging would be a promising tool for evaluating α4β2 nAChR availability in the mouse brain and may be useful in translational research focused on nAChR-related diseases. en-copyright= kn-copyright= en-aut-name=MatsuuraYuki en-aut-sei=Matsuura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaMasashi en-aut-sei=Ueda en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HigakiYusuke en-aut-sei=Higaki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeKeiko en-aut-sei=Watanabe en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HabaraShogo en-aut-sei=Habara en-aut-mei=Shogo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KaminoShinichiro en-aut-sei=Kamino en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SajiHideo en-aut-sei=Saji en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=EnomotoShuichi en-aut-sei=Enomoto en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= affil-num=8 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=5-[(123)I]iodo-3-(2(S)-azetidinylmethoxy)pyridine ([(123)I]5IA) kn-keyword=5-[(123)I]iodo-3-(2(S)-azetidinylmethoxy)pyridine ([(123)I]5IA) en-keyword=Alzheimer's disease kn-keyword=Alzheimer's disease en-keyword=Mouse kn-keyword=Mouse en-keyword=Nicotinic acetylcholine receptor (nAChR) kn-keyword=Nicotinic acetylcholine receptor (nAChR) en-keyword=Single-photon emission computed tomography (SPECT) kn-keyword=Single-photon emission computed tomography (SPECT) en-keyword=Tg2576 kn-keyword=Tg2576 END start-ver=1.4 cd-journal=joma no-vol=21 cd-vols= no-issue=3 article-no= start-page=519 end-page=528 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20180725 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of the Relationship Between Cognitive Impairment, Glycometabolism, and Nicotinic Acetylcholine Receptor Deficits in a Mouse Model of Alzheimer's Disease en-subtitle= kn-subtitle= en-abstract= kn-abstract=PURPOSE:
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).
PROCEDURES:
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: α4β2 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 α7 nAChRs and N-methyl-D-aspartate receptors (NMDARs).
RESULTS:
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 α4 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 α7 nAChRs, or NMDARs were associated with cognitive impairments in APP/PS2 mice.
CONCLUSION:
A decrease in cerebral α4β2 nAChR density could act as a biomarker reflecting cognitive impairments associated with AD pathology. en-copyright= kn-copyright= en-aut-name=MatsuuraYuki en-aut-sei=Matsuura en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UedaMasashi en-aut-sei=Ueda en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HigakiYusuke en-aut-sei=Higaki en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SanoKohei en-aut-sei=Sano en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SajiHideo en-aut-sei=Saji en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=EnomotoShuichi en-aut-sei=Enomoto en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= affil-num=5 en-affil=Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= affil-num=6 en-affil=Department of Biofunction Imaging Analysis, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Alzheimer's disease kn-keyword=Alzheimer's disease en-keyword=Nicotinic acetylcholine receptors kn-keyword=Nicotinic acetylcholine receptors en-keyword=2-Deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) kn-keyword=2-Deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) en-keyword= 5-[I-123]Iodo-3-[2(S)-azetidinylmethoxy]pyridine ([I-123]5IA) kn-keyword= 5-[I-123]Iodo-3-[2(S)-azetidinylmethoxy]pyridine ([I-123]5IA) en-keyword=APP kn-keyword=APP en-keyword=PS2 mice kn-keyword=PS2 mice END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=165461 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=20140818 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Radiolabeled probes targeting hypoxia-inducible factor-1-active tumor microenvironments en-subtitle= kn-subtitle= en-abstract= kn-abstract= Because tumor cells grow rapidly and randomly, hypoxic regions arise from the lack of oxygen supply in solid tumors. Hypoxic regions in tumors are known to be resistant to chemotherapy and radiotherapy. Hypoxia-inducible factor-1 (HIF-1) expressed in hypoxic regions regulates the expression of genes related to tumor growth, angiogenesis, metastasis, and therapy resistance. Thus, imaging of HIF-1-active regions in tumors is of great interest. HIF-1 activity is regulated by the expression and degradation of its α subunit (HIF-1α), which is degraded in the proteasome under normoxic conditions, but escapes degradation under hypoxic conditions, allowing it to activate transcription of HIF-1-target genes. Therefore, to image HIF-1-active regions, HIF-1-dependent reporter systems and injectable probes that are degraded in a manner similar to HIF-1α have been recently developed and used in preclinical studies. However, no probe currently used in clinical practice directly assesses HIF-1 activity. Whether the accumulation of (18)F-FDG or (18)F-FMISO can be utilized as an index of HIF-1 activity has been investigated in clinical studies. In this review, the current status of HIF-1 imaging in preclinical and clinical studies is discussed. en-copyright= kn-copyright= en-aut-name=UedaMasashi en-aut-sei=Ueda en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SajiHideo en-aut-sei=Saji en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=12 cd-vols= no-issue=12 article-no= start-page=1338 end-page=1342 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20150928 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Histological and Nuclear Medical Comparison of Inflammation After Hemostasis with Non-Thermal Plasma and Thermal Coagulation en-subtitle= kn-subtitle= en-abstract= kn-abstract= The objective of this study is to examine the invasiveness of hemostasis by non-thermal plasma (NTP) compared with hemostasis by thermal coagulation (TC). The inflammation recovery process after hemostasis by TC and NTP was compared by using histological methods and nuclear medical molecular imaging. The necrotic areas in the NTP group disappeared after 5 days, whereas they remained 15 days after hemostasis in the TC group. The accumulation of 2-deoxy-2-[F-18] fluoro-D-glucopyranose (F-18-FDG), which reflects the existence of inflammatory cells, was higher in the TC group than in the NTP group on day 15. Thus, this study indicates that hemostasis by NTP is less inflammatory than TC. This report is the first to evaluate inflammation that occurred after hemostasis with medical devices noninvasively. en-copyright= kn-copyright= en-aut-name=UedaMasashi en-aut-sei=Ueda en-aut-mei=Masashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamagamiDaiki en-aut-sei=Yamagami en-aut-mei=Daiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=WatanabeKeiko en-aut-sei=Watanabe en-aut-mei=Keiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MoriAsami en-aut-sei=Mori en-aut-mei=Asami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimuraHiroyuki en-aut-sei=Kimura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SanoKohei en-aut-sei=Sano en-aut-mei=Kohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SajiHideo en-aut-sei=Saji en-aut-mei=Hideo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=IshikawaKenji en-aut-sei=Ishikawa en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HoriMasaru en-aut-sei=Hori en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SakakitaHajime en-aut-sei=Sakakita en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IkeharaYuzuru en-aut-sei=Ikehara en-aut-mei=Yuzuru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=EnomotoShuichi en-aut-sei=Enomoto en-aut-mei=Shuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutica Science, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutica Science, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutica Science, Okayama University kn-affil= affil-num=4 en-affil=Radioisotope Research Center, Kyoto University kn-affil= affil-num=5 en-affil=Radioisotope Research Center, Kyoto University kn-affil= affil-num=6 en-affil=Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= affil-num=7 en-affil=Graduate School of Pharmaceutical Sciences, Kyoto University kn-affil= affil-num=8 en-affil=Graduate School of Engineering, Nagoya University kn-affil= affil-num=9 en-affil=Graduate School of Engineering, Nagoya University kn-affil= affil-num=10 en-affil=National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=11 en-affil=National Institute of Advanced Industrial Science and Technology kn-affil= affil-num=12 en-affil=Graduate School of Medicine, Dentistry, and Pharmaceutica Science, Okayama University kn-affil= en-keyword=hemostasis kn-keyword=hemostasis en-keyword=imaging kn-keyword=imaging en-keyword=inflammation kn-keyword=inflammation en-keyword=non-thermal plasma kn-keyword=non-thermal plasma en-keyword=positron emission tomography kn-keyword=positron emission tomography END