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Article ; Online: Preclinical validation of a novel brain-penetrant PET ligand for visualization of histone deacetylase 6: a potential imaging target for neurodegenerative diseases.

Tago, Tetsuro / Sakata, Muneyuki / Kanazawa, Masakatsu / Yamamoto, Shigeyuki / Ishii, Kenji / Toyohara, Jun

European journal of nuclear medicine and molecular imaging

2024

Abstract: Purpose: Histone deacetylase 6 (HDAC6) has emerged as a therapeutic target for neurodegenerative diseases such as Alzheimer's disease. Noninvasive imaging of HDAC6 in the brain by positron emission tomography (PET) would accelerate research into its ... ...

Abstract	Purpose: Histone deacetylase 6 (HDAC6) has emerged as a therapeutic target for neurodegenerative diseases such as Alzheimer's disease. Noninvasive imaging of HDAC6 in the brain by positron emission tomography (PET) would accelerate research into its roles in these diseases. We recently discovered an Methods: Process validation of [ Results: Three consecutive validation runs of the automated radiosynthesis gave [ Conclusion: These results support the clinical utility of [
Language	English
Publishing date	2024-03-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	8236-3
ISSN	1619-7089 ; 0340-6997 ; 1619-7070
ISSN (online)	1619-7089
ISSN	0340-6997 ; 1619-7070
DOI	10.1007/s00259-024-06666-1
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Article ; Online: Biodistribution assessment of cationic pullulan nanogel, a nasal vaccine delivery system, in mice and non-human primates

Yuki, Yoshikazu / Harada, Norihiro / Sawada, Shin-ichi / Uchida, Yohei / Nakahashi-Ouchida, Rika / Mori, Hiromi / Yamanoue, Tomoyuki / Machita, Tomonori / Kanazawa, Masakatsu / Fukumoto, Dai / Ohba, Hiroyuki / Miyazaki, Takashi / Akiyoshi, Kazunari / Fujihashi, Kohtaro / Kiyono, H.

Vaccine. 2023 June 27,

2023

Abstract: Cationic cholesteryl-group–bearing pullulan nanogel (cCHP-nanogel) is an effective drug-delivery system for nasal vaccines. However, cCHP-nanogel-based nasal vaccines might access the central nervous system due to its close proximity via the olfactory ... ...

Abstract	Cationic cholesteryl-group–bearing pullulan nanogel (cCHP-nanogel) is an effective drug-delivery system for nasal vaccines. However, cCHP-nanogel-based nasal vaccines might access the central nervous system due to its close proximity via the olfactory bulb in the nasal cavity. Using real-time quantitative tracking of the nanogel-based nasal botulinum neurotoxin and pneumococcal vaccines, we previously confirmed the lack of deposition of vaccine antigen in the cerebrum or olfactory bulbs of mice and non-human primates (NHPs), rhesus macaques. Here, we used positron emission tomography to investigate the biodistribution of the drug-delivery system itself, cCHP-nanogel after mice and NHPs were nasally administered with ¹⁸F-labeled cCHP nanogel. The results generated by the PET analysis of rhesus macaques were consistent with the direct counting of radioactivity due to ¹⁸F or ¹¹¹In in dissected mouse tissues. Thus, no depositions of cCHP-nanogel were noted in the cerebrum, olfactory bulbs, or eyes of both species after nasal administration of the radiolabeled cCHP-nanogel compound. Our findings confirm the safe biodistribution of the cCHP-nanogel-based nasal vaccine delivery system in mice and NHPs.
Keywords	Streptococcus pneumoniae ; antigens ; botulinum toxin ; cerebrum ; intranasal administration ; mice ; nanogels ; nasal cavity ; olfactory bulb ; positron-emission tomography ; pullulan ; radioactivity ; radiolabeling ; vaccines ; Nasal vaccine ; Drug delivery system ; Positron emission tomography (PET) ; Biodistribution ; Mouse ; Non-human primate ; cCHP nanogel ; CDI ; CHI ; CNS ; CHP ; DDS ; DOTA-NHS-ester ; HPLC ; K[2,2,2] ; LNP ; MRI ; NALT ; NHP ; OB ; PBS ; percent ID (%ID) ; PET ; PspA ; SFB ; SUV ; TSTU
Language	English
Dates of publication	2023-0627
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2023.06.065
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Zs.MO 458: Show issues

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Article ; Online: Biodistribution assessment of cationic pullulan nanogel, a nasal vaccine delivery system, in mice and non-human primates.

Yuki, Yoshikazu / Harada, Norihiro / Sawada, Shin-Ichi / Uchida, Yohei / Nakahashi-Ouchida, Rika / Mori, Hiromi / Yamanoue, Tomoyuki / Machita, Tomonori / Kanazawa, Masakatsu / Fukumoto, Dai / Ohba, Hiroyuki / Miyazaki, Takashi / Akiyoshi, Kazunari / Fujihashi, Kohtaro / Kiyono, Hiroshi

Vaccine

2023 Volume 41, Issue 34, Page(s) 4941–4949

Abstract: Cationic cholesteryl-group-bearing pullulan nanogel (cCHP-nanogel) is an effective drug-delivery system for nasal vaccines. However, cCHP-nanogel-based nasal vaccines might access the central nervous system due to its close proximity via the olfactory ... ...

Abstract	Cationic cholesteryl-group-bearing pullulan nanogel (cCHP-nanogel) is an effective drug-delivery system for nasal vaccines. However, cCHP-nanogel-based nasal vaccines might access the central nervous system due to its close proximity via the olfactory bulb in the nasal cavity. Using real-time quantitative tracking of the nanogel-based nasal botulinum neurotoxin and pneumococcal vaccines, we previously confirmed the lack of deposition of vaccine antigen in the cerebrum or olfactory bulbs of mice and non-human primates (NHPs), rhesus macaques. Here, we used positron emission tomography to investigate the biodistribution of the drug-delivery system itself, cCHP-nanogel after mice and NHPs were nasally administered with
MeSH term(s)	Animals ; Nanogels ; Macaca mulatta ; Tissue Distribution ; Drug Delivery Systems ; Administration, Intranasal ; Pneumococcal Vaccines
Chemical Substances	polyethylene glycol polyethyleneimine nanogel ; Nanogels ; pullulan (8ZQ0AYU1TT) ; Pneumococcal Vaccines
Language	English
Publishing date	2023-06-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2023.06.065
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Zs.MO 458: Show issues

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Article: Evaluation of D-isomers of 4-borono-2-

Kanazawa, Masakatsu / Nishiyama, Shingo / Hashimoto, Fumio / Kakiuchi, Takeharu / Tsukada, Hideo

EJNMMI research

2018 Volume 8, Issue 1, Page(s) 47

Abstract: Background: The potential of the D-isomerization of 4-borono-2-: Results: Tissue dissection analyses showed that D-: Conclusions: The present results indicate that D- ...

Abstract	Background: The potential of the D-isomerization of 4-borono-2- Results: Tissue dissection analyses showed that D- Conclusions: The present results indicate that D-
Language	English
Publishing date	2018-06-13
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2619892-7
ISSN	2191-219X
ISSN	2191-219X
DOI	10.1186/s13550-018-0404-6
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Article ; Online: Differences in in vitro microglial accumulation of the energy metabolism tracers [

Suzuki, Chie / Han, Sarina / Kesavamoorthy, Gandhervin / Kosugi, Mutsumi / Araki, Kaori / Harada, Norihiro / Kanazawa, Masakatsu / Tsukada, Hideo / Magata, Yasuhiro / Ouchi, Yasuomi

Scientific reports

2021 Volume 11, Issue 1, Page(s) 13200

Abstract: The positron emission tomography probes 2-deoxy-2-[ ...

Abstract	The positron emission tomography probes 2-deoxy-2-[
MeSH term(s)	Animals ; Cell Line ; Electron Transport Complex I/metabolism ; Energy Metabolism/physiology ; Fluorodeoxyglucose F18/metabolism ; Glucose/metabolism ; Glycolysis/physiology ; Interleukin-4/metabolism ; Lipopolysaccharides/pharmacology ; Mice ; Microglia/metabolism ; Neurons/drug effects ; Neurons/metabolism ; Positron-Emission Tomography/methods ; Pyridines/metabolism ; Radiopharmaceuticals/metabolism ; Tomography, X-Ray Computed/methods
Chemical Substances	Il4 protein, mouse ; Lipopolysaccharides ; Pyridines ; Radiopharmaceuticals ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Interleukin-4 (207137-56-2) ; Electron Transport Complex I (EC 7.1.1.2) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-06-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-92436-0
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Article: Effects of acetaminophen on mitochondrial complex I activity in the rat liver and kidney: a PET study with

Ohba, Hiroyuki / Kanazawa, Masakatsu / Kakiuchi, Takeharu / Tsukada, Hideo

EJNMMI research

2016 Volume 6, Issue 1, Page(s) 82

Abstract: Background: In the present study, 2-tert-butyl-4-chloro-5-[6-(4-: Results: The uptake of : Conclusions: The present study demonstrated ... ...

Abstract	Background: In the present study, 2-tert-butyl-4-chloro-5-[6-(4- Results: The uptake of Conclusions: The present study demonstrated that
Language	English
Publishing date	2016-11-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2619892-7
ISSN	2191-219X
ISSN	2191-219X
DOI	10.1186/s13550-016-0241-4
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Article ; Online: Effect of MPTP on Serotonergic Neuronal Systems and Mitochondrial Complex I Activity in the Living Brain: A PET Study on Conscious Rhesus Monkeys.

Kanazawa, Masakatsu / Ohba, Hiroyuki / Nishiyama, Shingo / Kakiuchi, Takeharu / Tsukada, Hideo

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2017 Volume 58, Issue 7, Page(s) 1111–1116

Abstract: The objective of the present PET study was to compare the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on serotonergic neuronal systems and mitochondrial complex I (MC-I) activity with that of dopamine in conscious rhesus monkeys ( ...

Abstract	The objective of the present PET study was to compare the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on serotonergic neuronal systems and mitochondrial complex I (MC-I) activity with that of dopamine in conscious rhesus monkeys (
MeSH term(s)	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Brain/diagnostic imaging ; Brain/drug effects ; Brain/metabolism ; Dopaminergic Neurons/drug effects ; Dopaminergic Neurons/metabolism ; Electron Transport Complex I/metabolism ; Macaca mulatta ; Male ; Molecular Imaging/methods ; Neurotoxins ; Parkinsonian Disorders/chemically induced ; Parkinsonian Disorders/diagnostic imaging ; Parkinsonian Disorders/metabolism ; Positron-Emission Tomography/methods ; Serotonergic Neurons/drug effects ; Serotonergic Neurons/metabolism ; Tissue Distribution
Chemical Substances	Neurotoxins ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (9P21XSP91P) ; Electron Transport Complex I (EC 1.6.5.3)
Language	English
Publishing date	2017-03-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.116.189159
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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 328: Show issues

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Article: Synthesis and evaluation of N-isopropyl-p-[

Toyohara, Jun / Harada, Norihiro / Kakiuchi, Takeharu / Ohba, Hiroyuki / Kanazawa, Masakatsu / Tago, Tetsuro / Sakata, Muneyuki / Ishiwata, Kiichi

EJNMMI research

2020 Volume 10, Issue 1, Page(s) 115

Abstract: Introduction: Increases in fasting plasma glucose (PG) levels lead to a decrease in 2-deoxy-2-[: Methods: We synthesized and evaluated N-isopropyl-p-[: Results: [: Conclusion: [ ...

Abstract	Introduction: Increases in fasting plasma glucose (PG) levels lead to a decrease in 2-deoxy-2-[ Methods: We synthesized and evaluated N-isopropyl-p-[ Results: [ Conclusion: [
Language	English
Publishing date	2020-10-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2619892-7
ISSN	2191-219X
ISSN	2191-219X
DOI	10.1186/s13550-020-00702-5
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Article ; Online: In vivo alterations of mitochondrial activity and amyloidosis in early-stage senescence-accelerated mice: a positron emission tomography study.

Yamagishi, Satoru / Iga, Yurika / Ikegaya, Shunsuke / Kakiuchi, Takeharu / Ohba, Hiroyuki / Nishiyama, Shingo / Fukomoto, Daisuke / Kanazawa, Masakatsu / Harada, Norihiro / Tsukada, Hideo / Sato, Kohji / Ouchi, Yasuomi

Journal of neuroinflammation

2021 Volume 18, Issue 1, Page(s) 288

Abstract: Purpose: While marked reductions in neural activity and mitochondrial function have been reported in Alzheimer's disease (AD), the degree of mitochondrial activity in mild cognitive impairment (MCI) or early-stage AD remains unexplored. Here, we used ... ...

Abstract	Purpose: While marked reductions in neural activity and mitochondrial function have been reported in Alzheimer's disease (AD), the degree of mitochondrial activity in mild cognitive impairment (MCI) or early-stage AD remains unexplored. Here, we used positron emission tomography (PET) to examine the direct relationship between mitochondrial activity ( Methods: Five- to 25-week-old SAMP10 and control SAMR1 mice, were used in the experiments. PET was used to measure the binding levels (standard uptake value ratios; SUVRs) of [ Results: The SUVR of Conclusion: The present results provide in vivo evidence of a decrease in mitochondrial energy production and elevated amyloidosis at an early stage in SAMP10 mice. The inverse correlation between these two phenomena suggests a concurrent change in neuronal energy failure by Aβ-induced elevation of neuroinflammatory responses. Comparison of PET data with histological findings suggests that temporal increase of ATPB level may not be neurofunctionally implicated during neuropathological processes, including Aβ pathology, in an animal model of early-phase AD spectrum disorder.
MeSH term(s)	Aging/genetics ; Aging/metabolism ; Aging/pathology ; Amyloidosis/genetics ; Amyloidosis/metabolism ; Amyloidosis/pathology ; Animals ; Brain/metabolism ; Brain/pathology ; Mice ; Mice, Transgenic ; Mitochondria/genetics ; Mitochondria/metabolism ; Mitochondria/pathology ; Positron-Emission Tomography/methods
Language	English
Publishing date	2021-12-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2156455-3
ISSN	1742-2094 ; 1742-2094
ISSN (online)	1742-2094
ISSN	1742-2094
DOI	10.1186/s12974-021-02343-4
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Article ; Online: Monitoring Mitochondrial Complex-I Activity Using Novel PET Probe 18F-BCPP-EF Allows Early Detection of Radiotherapy Effect in Murine Squamous Cell Carcinoma.

Murayama, Chieko / Kawaguchi, Akira T / Kamijo, Akemi / Naito, Katsuko / Kanazawa, Masakatsu / Tsukada, Hideo

PloS one

2017 Volume 12, Issue 1, Page(s) e0170911

Abstract: Objectives: Aerobic glycolysis, the main pathway of energy production in tumors (Warburg effect) allows detection of tumors by positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (18F-FDG). Since ionizing radiation (IR) is reported to ... ...

Abstract	Objectives: Aerobic glycolysis, the main pathway of energy production in tumors (Warburg effect) allows detection of tumors by positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (18F-FDG). Since ionizing radiation (IR) is reported to switch aerobic glycolysis to mitochondrial oxidative phosphorylation, radiotherapeutic efficacy was monitored by the activity of mitochondrial complex I (MC-I), using a new PET probe 18F-BCPP-EF, 18F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoro-ethoxy)-ethoxy] -pyridine-3-ylmethoxy}-2H-pyridazin-3-one, compared with 18F-FDG uptake and the apoptosis index. Methods: Tumor uptake of 18F-BCPP-EF or 18F-FDG was examined in C3H/HeN mice inoculated with murine squamous cell carcinoma SCCVII at various time points after a single dose of x-ray irradiation at 0, 6, 15, or 30 Gy. Apoptosis incidence was determined by TUNEL staining in excised tumor tissue. Results: Tumor growth suppression was dose-dependent; tumor grew 10-fold (0 Gy), 5-fold (6 Gy), 2-fold (15 Gy), and reduced to half in its volume (30 Gy) 14 days after treatment. 18F-BCPP-EF uptake was significantly increased as early as 3 days after 15 Gy or 30 Gy, when tumor size and apoptosis index showed no difference among radiation doses. In contrast, 18F-FDG uptake was initially increased dose-dependently, remained elevated up to 7 days, and eventually decreased 10 days after 30 Gy and also 14 days after 15 Gy when tumor size was already reduced. Apoptosis index was increased after irradiation but failed to correlate with tumor response. Conclusion: Tumor uptake of 18F-BCPP-EF was increased dose-dependently early after effective doses of IR when 18F-FDG uptake as well as apoptosis incidence were not indicative of tumor response. The results suggest that 18F-BCPP-EF is a promising "positive" MC-I imaging PET probe for early detection of efficacy of tumor radiotherapy.
MeSH term(s)	Animals ; Apoptosis/radiation effects ; Carcinoma, Squamous Cell/diagnostic imaging ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/radiotherapy ; Electron Transport Complex I/metabolism ; Fluorodeoxyglucose F18 ; Mice ; Mice, Inbred C3H ; Neoplasm Transplantation ; Positron-Emission Tomography ; Pyridazines ; Pyridines ; Radiopharmaceuticals
Chemical Substances	2-tert-butyl-4-chloro-5-(6-(2-(2-fluoroethoxy)ethoxy)pyridin-3-ylmethoxy)-2H-pyridazin-3-one ; Pyridazines ; Pyridines ; Radiopharmaceuticals ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Electron Transport Complex I (EC 1.6.5.3)
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0170911
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