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2. Histamine and Microglia

Author

Iida, Tomomitsu, Yanai, Kazuhiko, Yoshikawa, Takeo, Geyer, Mark A., Series Editor, Marsden, Charles A., Series Editor, Ellenbroek, Bart A., Series Editor, Barnes, Thomas R. E., Series Editor, Andersen, Susan L., Series Editor, Paulus, Martin P., Series Editor, Yanai, Kazuhiko, editor, and Passani, Maria Beatrice, editor

Published
2022
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4. Histamine Neuroimaging in Stress-Related Disorders

Author

Fukudo, Shin, Kano, Michiko, Sato, Yasuhiro, Muratsubaki, Tomohiko, Kanazawa, Motoyori, Tashiro, Manabu, Yanai, Kazuhiko, Geyer, Mark A., Series Editor, Marsden, Charles A., Series Editor, Ellenbroek, Bart A., Series Editor, Barnes, Thomas R. E., Series Editor, Andersen, Susan L., Series Editor, Paulus, Martin P., Series Editor, Yanai, Kazuhiko, editor, and Passani, Maria Beatrice, editor

Published
2022
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10. Dynamic PET Measures of Tau Accumulation in Cognitively Normal Older Adults and Alzheimer’s Disease Patients Measured Using [18F] THK-5351

Author

Lockhart, Samuel N, Baker, Suzanne L, Okamura, Nobuyuki, Furukawa, Katsutoshi, Ishiki, Aiko, Furumoto, Shozo, Tashiro, Manabu, Yanai, Kazuhiko, Arai, Hiroyuki, Kudo, Yukitsuka, Harada, Ryuichi, Tomita, Naoki, Hiraoka, Kotaro, Watanuki, Shoichi, and Jagust, William J

Subjects
Biological Psychology, Psychology, Biomedical Imaging, Dementia, Neurosciences, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Alzheimer's Disease, Aging, Neurodegenerative, Brain Disorders, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Aged, Alzheimer Disease, Aminopyridines, Biomarkers, Brain, Brain Mapping, Case-Control Studies, Cognition, Fluorine Radioisotopes, Frontal Lobe, Humans, Positron-Emission Tomography, Quinolines, Temporal Lobe, Time Factors, tau Proteins, General Science & Technology
Abstract

Background[18F]THK5351, a recently-developed positron emission tomography (PET) tracer for measuring tau neurofibrillary tangle accumulation, may help researchers examine aging, disease, and tau pathology in living human brains. We examined THK5351 tracer pharmacokinetics to define an optimal acquisition time for static late images.MethodsPrimary measurements were calculation of regional values of distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) in 6 healthy older control and 10 Alzheimer's disease (AD) participants. We examined associations between DVR and SUVR, searching for a 20 min SUVR time window that was stable and comparable to DVR. We additionally examined diagnostic group differences in this 20 min SUVR.ResultsIn healthy controls, [18F]THK5351 uptake was low, with increased temporal relative to frontal binding. In AD, regional uptake was substantially higher than in healthy controls, with temporal exceeding frontal binding. Retention in cerebellar gray matter, which was used as the reference region, was low compared to other regions. Both DVR and SUVR values showed minimal change over time after 40 min. SUVR 20-40, 30-50, and 40-60 min were most consistently correlated with DVR; SUVR 40-60 min, the most stable time window, was used in further analyses. Significant (AD > healthy control) group differences existed in temporoparietal regions, with marginal medial temporal differences. We found high basal ganglia SUVR 40-60 min signal, with no group differences.ConclusionsWe examined THK5351, a new PET tracer for measuring tau accumulation, and compared multiple analysis methods for quantifying regional tracer uptake. SUVR 40-60 min performed optimally when examining 20 min SUVR windows, and appears to be a practical method for quantifying relative regional tracer retention. The results of this study offer clinical potential, given the usefulness of THK5351-PET as a biomarker of tau pathology in aging and disease.

Published
2016

15. Histamine Clearance Through Polyspecific Transporters in the Brain

Author

Yoshikawa, Takeo, Yanai, Kazuhiko, Barrett, James E., Editor-in-chief, Flockerzi, Veit, Series editor, Frohman, Michael A., Series editor, Geppetti, Pierangelo, Series editor, Hofmann, Franz B., Series editor, Michel, Martin C., Series editor, Page, Clive P, Series editor, Rosenthal, Walter, Series editor, Wang, KeWei, Series editor, Hattori, Yuichi, editor, and Seifert, Roland, editor

Published
2017
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19. Tau positron emission tomography using [18F]THK5351 and cerebral glucose hypometabolism in Alzheimer's disease

Author

Kang, Jae Myeong, Lee, Sang-Yoon, Seo, Seongho, Jeong, Hye Jin, Woo, Sung-Ho, Lee, Hyon, Lee, Yeong-Bae, Yeon, Byeong Kil, Shin, Dong Hoon, Park, Kee Hyung, Kang, Hyejin, Okamura, Nobuyuki, Furumoto, Shozo, Yanai, Kazuhiko, Villemagne, Victor L., Seong, Joon-Kyung, Na, Duk L., Ido, Tatsuo, Cho, Jaelim, Lee, Kyoung-Min, and Noh, Young

Published
2017
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29. PET Studies of Brain Metabolism in Exercise Research

Author

Tashiro, Manabu, Fujimoto, Toshihiko, Masud, Mohammad Mehedi, Khondkar, Sabina, Watanuki, Shoichi, Yanai, Kazuhiko, Itoh, Masatoshi, Ishii, Keizo, Boecker, Henning, editor, Hillman, Charles H., editor, Scheef, Lukas, editor, and Strüder, Heiko K., editor

Published
2012
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36. Evaluation of 18F labeled glial fibrillary acidic protein binding nanobody and its brain shuttle peptide fusion proteins using a neuroinflammation rat model.

Author

Morito, Takahiro, Harada, Ryuichi, Iwata, Ren, Ishikawa, Yoichi, Okamura, Nobuyuki, Kudo, Yukitsuka, Furumoto, Shozo, Yanai, Kazuhiko, and Tashiro, Manabu

Subjects
GLIAL fibrillary acidic protein, CHIMERIC proteins, PEPTIDES, TRANSLOCATOR proteins, PROTEIN binding, ANIMAL disease models
Abstract

Astrogliosis is a crucial feature of neuroinflammation and is characterized by the significant upregulation of glial fibrillary acidic protein (GFAP) expression. Hence, visualizing GFAP in the living brain of patients with damaged central nervous system using positron emission tomography (PET) is of great importance, and it is expected to depict neuroinflammation more directly than existing neuroinflammation imaging markers. However, no PET radiotracers for GFAP are currently available. Therefore, neuroimaging with antibody-like affinity proteins could be a viable strategy for visualizing imaging targets that small molecules rarely recognize, such as GFAP, while we need to overcome the challenges of slow clearance and low brain permeability. The E9 nanobody, a small-affinity protein with high affinity and selectivity for GFAP, was utilized in this study. E9 was engineered by fusing a brain shuttle peptide that facilitates blood-brain barrier permeation via two different types of linker domains: E9-GS-ApoE (EGA) and E9-EAK-ApoE (EEA). E9, EGA and EEA were radiolabeled with fluorine-18 using cell-free protein radiosynthesis. In vitro autoradiography showed that all radiolabeled proteins exhibited a significant difference in neuroinflammation in the brain sections created from a rat model constructed by injecting lipopolysaccharide (LPS) into the unilateral striatum of wildtype rats, and an excess competitor displaced their binding. However, exploratory in vivo PET imaging and ex vivo biodistribution studies in the rat model failed to distinguish neuroinflammatory lesions within 3 h of 18F-EEA intravenous injection. This study contributes to a better understanding of the characteristics of small-affinity proteins fused with a brain shuttle peptide for further research into the use of protein molecules as PET tracers for imaging neuropathology. [ABSTRACT FROM AUTHOR]

Published
2023
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