BackgroundSeveral studies have demonstrated that repetitive transcranial magnetic stimulation (rT... more BackgroundSeveral studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) elicits moderate antidepressant effects. Several previous studies suggested that the dopaminergic system might be related to this therapeutic action of rTMS. We attempted to determine the effects of chronic rTMS on central dopaminergic function in depression using positron emission tomography (PET) with [11C]raclopride.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 16, 2015
Tau accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD) and othe... more Tau accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD) and other tauopathies. Quantitative visualization of tau pathology in humans can be a powerful method as a diagnostic aid and for monitoring potential therapeutic interventions. We established methods of PET quantification of tau pathology in human brain with (11)C-PBB3 considering its radiometabolite entering the brain. Seven AD and seven healthy subjects underwent dynamic (11)C-PBB3 PET scanning. Arterial blood was sampled to obtain the parent and metabolite input functions. Quantification of (11)C-PBB3 binding was performed using the dual-input models that take the brain metabolite activity into consideration, traditional single-input models without such considerations, and the reference tissue model (MRTMO) and standardized uptake value ratio (SUVR) without requiring blood data. The cerebellar cortex was used as reference tissue for all methods. The dual-input graphical models estimated bind...
International journal of geriatric psychiatry, Jan 21, 2014
We examined patients with mild cognitive impairment (MCI) with a history of geriatric depression ... more We examined patients with mild cognitive impairment (MCI) with a history of geriatric depression (GD) and healthy controls (HC) to evaluate the effect of beta-amyloid (Aβ) pathology on the pathology of GD by using [(18) F]florbetapir PET. Thirty-three elderly patients (76.7 ± 4.2 years) and 22 healthy controls (HC; 72.0 ± 4.5 years, average ± SD) were examined by [(18) F]florbetapir positron emission tomography (PET) to quantify the standard uptake value ratio (SUVR) as the degree of amyloid accumulation, by MRI to determine the degree of atrophy, by Mini-Mental State Examination for cognitive functions, and by Geriatric Depression Scale for the severity of depression, and by Clinical Dementia Rating for activity of daily living (ADL). The cut-off value of 1.08 for SUVR was defined as Aβ-positive. Of the patients and HC, 39.4% and 27.3%, respectively, were beta-amyloid-positive. The onset age of GD was significantly correlated with SUVR (r = 0.44, p < 0.01). Compared to patients ...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2014
Central substance P receptors, termed NK-1 receptors, have been considered as therapeutic targets... more Central substance P receptors, termed NK-1 receptors, have been considered as therapeutic targets in the development of drugs against diverse conditions, including emesis, overactive bladder, and depression. Here, we applied small animal positron emission tomography (PET) and a radioligand for NK-1 receptors ([(18)F]FE-SPA-RQ) for measuring occupancies of these receptors by a selective antagonist (aprepitant) in order to examine the validity of this in vivo imaging system for preclinical characterization of candidate agents acting on NK-1 receptors, and as a tool for predicting optimal doses in humans. PET in gerbils depicted high uptake in the striatum and dose-dependent displacement with increasing doses of aprepitant. Occupancies increased as a function of aprepitant plasma concentrations according to a one-site competition model, which agrees with reported occupancy-concentration relationships in clinical studies after correction for species differences in plasma protein-unbound...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2014
Norepinephrine transporter (NET) plays important roles in the treatment of various neuropsychiatr... more Norepinephrine transporter (NET) plays important roles in the treatment of various neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder (ADHD). Nortriptyline is a NET-selective tricyclic antidepressant (TCAs) that has been widely used for the treatment of depression. Previous positron emission tomography (PET) studies have reported over 80% serotonin transporter occupancy with clinical doses of selective serotonin reuptake inhibitors (SSRIs), but there has been no report of NET occupancy in patients treated with relatively NET-selective antidepressants. In the present study, we used PET and (S,S)-[18¹⁸F]FMeNER-D₂ to investigate NET occupancies in the thalamus in 10 patients with major depressive disorder taking various doses of nortriptyline, who were considered to be responders to the treatment. Reference data for the calculation of occupancy were derived from age-matched healthy controls. The result showed approximately 50-70% NET occupancies...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 1999
The aim of the present study was to quantify the density and affinity of human extrastriatal dopa... more The aim of the present study was to quantify the density and affinity of human extrastriatal dopamine D2 receptors using positron emission tomography (PET). [(11)C]FLB-457, a high-affinity dopamine D2 receptor antagonist with various specific radioactivities (SA) was used. Eight healthy male subjects, age 20-35 yr, participated twice or three times at different SAs (1-279 GBq/ µmol), and serial dynamic scans were performed in the 3D data acquisition mode. The peak of the specific binding was not well defined with high SA due to the flatness of the curves after 60 min but was observed within the PET measurement. In the experiment with low SA, the peak came earlier than that with high SA. Scatchard analysis was performed using the maximal specific binding value (transient equilibrium) and the radioactivity in the cerebellum as free ligand concentration. The highest density was observed in the thalamus (2.3+/-0.6 pmol/ml), followed by the temporal cortex (1.5+/-0.5 pmol/ml), hippocampu...
Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease is a progressive dementia that is characterized by a loss of recent memory. Evidence has accumulated to support the hypothesis that synapses are critical storage sites for memory. However, it is still uncertain whether tau protein is involved in associative memory storage and whether tau is distributed in mature brain synapses. To address this question, we examined the synaptosomal distribution of tau protein in both JNPL3 transgenic mice expressing human P301L tau and non-transgenic littermates. The JNPL3 mouse line is known as one of the mouse models of human tauopathy that develop motor and behavioral deficits with intracellular tau aggregates in the spinal cord and brainstem. The phenotype of disease progression is highly dependent on strain background. In this study, we confirmed that male JNPL3 transgenic mice with C57BL/6J strain background showed neither any sign of motor deficits nor accumulation of hyperphosphorylated tau in the sarkosyl-insoluble fraction until 18 months of age. Subcellular fractionation analysis showed that both mouse tau and human P301L tau were present in the synaptosomal fraction. Those tau proteins were less-phosphorylated than tau in the cytosolic fraction. Human P301L tau was preferentially distributed in the synaptosomal fraction while mouse endogenous tau was more distributed in the cytosolic fraction. Interestingly, a human-specific tau band with phosphorylation at Ser199 and Ser396 was observed in the synaptosomal fraction of JNPL3 mice. This tau was not identical to either tau species in cytosolic fraction or a prominent hyperphosphorylated 64 kDa tau species that was altered to tau pathology. These results suggest that exogenous human P301L tau induces synaptosomal distribution of tau protein with a certain phosphorylation. Regulating the synaptosomal tau level might be a potential target for a therapeutic intervention directed at preventing neurodegeneration.
Vocalizations of common marmoset (Callithrix jacchus) were examined under experimental situations... more Vocalizations of common marmoset (Callithrix jacchus) were examined under experimental situations related to fear or anxiety. When marmosets were isolated in an unfamiliar environment, they frequently vocalized &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;tsik-egg&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; calls, which were the combination calls of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;tsik&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; followed by several &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;egg&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;. Tsik-egg calls were also observed after treatment with the anxiogenic drug FG-7142 (20mg/kg, sc). In contrast, when marmosets were exposed to predatory stimuli as fear-evoking situations, they frequently vocalized tsik solo calls as well as tsik-egg calls. These results suggest that marmosets dissociate the vocalization of tsik-egg and tsik calls under conditions related to fear/anxiety; tsik-egg solo vocalizations were emitted under anxiety-related conditions (e.g., isolation and anxiogenic drug treatment), whereas a mixed vocalization of tsik-egg and tsik was emitted when confronted with fear-provoking stimuli (i.e., threatening predatory stimuli). Tsik-egg call with/without tsik can be used as a specific vocal index of fear/anxiety in marmosets, which allows us to understand the neural mechanism of negative emotions in primate.
Dissociative amnesia is characterized by an inability to retrieve information already saved in me... more Dissociative amnesia is characterized by an inability to retrieve information already saved in memories. 5-HT has some role in neural regulatory control and may be related to the recovery from dissociative amnesia. To examine the role of 5-HT1A receptors in the recovery from dissociative amnesia, we performed two positron emission tomography (PET) scans on a 30-year-old patient of dissociative amnesia using [(11)C]WAY-100635, the first at amnesic state, and the second at the time he had recovered. Exploratory voxel-based analysis (VBA) was performed using SPM software. 5-HT1A BPND images were compared between the patient at amnesic and recovery states and healthy subjects (14 males, mean age 29.8 ± 6.45) with Jack-knife analysis. 5-HT1A receptor bindings of the patient at the recovery state were significantly higher than those of healthy subjects in the right superior and middle frontal cortex, left inferior frontal and orbitofrontal cortex and bilateral inferior temporal cortex. Th...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014
2-((1E,3E)-4-(6-((11)C-methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol ((11)C-PBB3)... more 2-((1E,3E)-4-(6-((11)C-methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol ((11)C-PBB3) is a clinically useful PET probe that we developed for in vivo imaging of tau pathology in the human brain. To ensure the availability of this probe among multiple PET facilities, in the present study we established protocols for the radiosynthesis and quality control of (11)C-PBB3 and for the characterization of its photoisomerization, biodistribution, and metabolism. (11)C-PBB3 was synthesized by reaction of the tert-butyldimethylsilyl desmethyl precursor ( 1: ) with (11)C-methyl iodide using potassium hydroxide as a base, followed by deprotection. Photoisomerization of (11)C-PBB3 under fluorescent light was determined. The biodistribution and metabolite analysis of (11)C-PBB3 was determined in mice using the dissection method. (11)C-PBB3 was synthesized with 15.4% ± 2.8% radiochemical yield (decay-corrected, n = 50) based on the cyclotron-produced (11)C-CO2 and showed an averaged syn...
The discovery of tau mutations in frontotemporal dementia has been a key event in neurodegenerati... more The discovery of tau mutations in frontotemporal dementia has been a key event in neurodegenerative disease research. The rTg4510 mouse line expressing human tau with P301L FTDP-17-tau mutation has been established to understand the role of tau in neurodegeneration. Our histological analyses with tau antibodies and fluorescent tau ligands on rTg4510 mice revealed that tau oligomer formation was distinct from tangle formation. While in vivo imaging of mature tangles is now available, imaging biomarkers for tau oligomers would be useful for clarifying their roles in neurotoxicity and for diagnosing early-stage tau pathology.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
Noninvasive determination of amyloid-β peptide (Aβ) deposition has important significance for ear... more Noninvasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention for Alzheimer's disease (AD). In the present study, we investigated the availability of radiolabeled DRM106 ((123/125)I-DRM106 [6-iodo-2-[4-(1H-3-pyrazolyl)phenyl]imidazo[1,2-a]pyridine]), a compound with sufficient affinity for the synthesis of human Aβ fibrils and satisfactory metabolic stability, as a SPECT ligand in living brains. The sensitivity of (125)I-DRM106 for detecting Aβ deposition was compared with that of (125)I-IMPY (2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), a well-known amyloid SPECT ligand, by ex vivo autoradiographic analyses in 18-mo-old amyloid precursor protein transgenic mice. To verify the sensitivity and quantitation of radiolabeled DRM106 for in vivo imaging, we compared the detectability of Aβ plaques with (123)I-DRM106 and a well-known amyloid PET agent, (11)C-labeled Pittsburgh compound B ((11)C-P...
Abstract: Earlier in vivo PET experiments have demonstrated the binding of the neuroprotective al... more Abstract: Earlier in vivo PET experiments have demonstrated the binding of the neuroprotective alkaloid vinpocetine to the peripheral benzodiazepine receptor (PBR) or, with other terminology, the TSPO (18kDa translocator protein). With the aim of ...
Dementia, a progressive cognitive decline, leads to a gradually increasing restriction of daily a... more Dementia, a progressive cognitive decline, leads to a gradually increasing restriction of daily activities. Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) is the most common form of dementia. The pathological features of AD include plaques and tangles which are constituted by amyloid beta peptide (A beta) and tau protein. These amyloidogenic molecules have been mechanistically implicated in the pathogenesis of AD and related neurodegenerative dementias. The key strategy for establishment of diagnostic and therapeutic approaches to AD is sensitive and specific detection of the incipient neuropathology characteristics of AD, combined with emerging treatments that counteract molecular processes in AD pathogenesis. Recent advances in molecular imaging research have enabled visualization of brain amyloidosis. The rapid development of different compounds suitable for visualizing amyloid would permit pathology-specific diagnosis of AD at an asymptomatic stage in a noninvasive manner, and could also allow early immunotherapeutic intervention without causing an excessive neuroinflammatory response.
BackgroundSeveral studies have demonstrated that repetitive transcranial magnetic stimulation (rT... more BackgroundSeveral studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) elicits moderate antidepressant effects. Several previous studies suggested that the dopaminergic system might be related to this therapeutic action of rTMS. We attempted to determine the effects of chronic rTMS on central dopaminergic function in depression using positron emission tomography (PET) with [11C]raclopride.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, Jan 16, 2015
Tau accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD) and othe... more Tau accumulation in the brain is a pathological hallmark of Alzheimer's disease (AD) and other tauopathies. Quantitative visualization of tau pathology in humans can be a powerful method as a diagnostic aid and for monitoring potential therapeutic interventions. We established methods of PET quantification of tau pathology in human brain with (11)C-PBB3 considering its radiometabolite entering the brain. Seven AD and seven healthy subjects underwent dynamic (11)C-PBB3 PET scanning. Arterial blood was sampled to obtain the parent and metabolite input functions. Quantification of (11)C-PBB3 binding was performed using the dual-input models that take the brain metabolite activity into consideration, traditional single-input models without such considerations, and the reference tissue model (MRTMO) and standardized uptake value ratio (SUVR) without requiring blood data. The cerebellar cortex was used as reference tissue for all methods. The dual-input graphical models estimated bind...
International journal of geriatric psychiatry, Jan 21, 2014
We examined patients with mild cognitive impairment (MCI) with a history of geriatric depression ... more We examined patients with mild cognitive impairment (MCI) with a history of geriatric depression (GD) and healthy controls (HC) to evaluate the effect of beta-amyloid (Aβ) pathology on the pathology of GD by using [(18) F]florbetapir PET. Thirty-three elderly patients (76.7 ± 4.2 years) and 22 healthy controls (HC; 72.0 ± 4.5 years, average ± SD) were examined by [(18) F]florbetapir positron emission tomography (PET) to quantify the standard uptake value ratio (SUVR) as the degree of amyloid accumulation, by MRI to determine the degree of atrophy, by Mini-Mental State Examination for cognitive functions, and by Geriatric Depression Scale for the severity of depression, and by Clinical Dementia Rating for activity of daily living (ADL). The cut-off value of 1.08 for SUVR was defined as Aβ-positive. Of the patients and HC, 39.4% and 27.3%, respectively, were beta-amyloid-positive. The onset age of GD was significantly correlated with SUVR (r = 0.44, p < 0.01). Compared to patients ...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2014
Central substance P receptors, termed NK-1 receptors, have been considered as therapeutic targets... more Central substance P receptors, termed NK-1 receptors, have been considered as therapeutic targets in the development of drugs against diverse conditions, including emesis, overactive bladder, and depression. Here, we applied small animal positron emission tomography (PET) and a radioligand for NK-1 receptors ([(18)F]FE-SPA-RQ) for measuring occupancies of these receptors by a selective antagonist (aprepitant) in order to examine the validity of this in vivo imaging system for preclinical characterization of candidate agents acting on NK-1 receptors, and as a tool for predicting optimal doses in humans. PET in gerbils depicted high uptake in the striatum and dose-dependent displacement with increasing doses of aprepitant. Occupancies increased as a function of aprepitant plasma concentrations according to a one-site competition model, which agrees with reported occupancy-concentration relationships in clinical studies after correction for species differences in plasma protein-unbound...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2014
Norepinephrine transporter (NET) plays important roles in the treatment of various neuropsychiatr... more Norepinephrine transporter (NET) plays important roles in the treatment of various neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder (ADHD). Nortriptyline is a NET-selective tricyclic antidepressant (TCAs) that has been widely used for the treatment of depression. Previous positron emission tomography (PET) studies have reported over 80% serotonin transporter occupancy with clinical doses of selective serotonin reuptake inhibitors (SSRIs), but there has been no report of NET occupancy in patients treated with relatively NET-selective antidepressants. In the present study, we used PET and (S,S)-[18¹⁸F]FMeNER-D₂ to investigate NET occupancies in the thalamus in 10 patients with major depressive disorder taking various doses of nortriptyline, who were considered to be responders to the treatment. Reference data for the calculation of occupancy were derived from age-matched healthy controls. The result showed approximately 50-70% NET occupancies...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 1999
The aim of the present study was to quantify the density and affinity of human extrastriatal dopa... more The aim of the present study was to quantify the density and affinity of human extrastriatal dopamine D2 receptors using positron emission tomography (PET). [(11)C]FLB-457, a high-affinity dopamine D2 receptor antagonist with various specific radioactivities (SA) was used. Eight healthy male subjects, age 20-35 yr, participated twice or three times at different SAs (1-279 GBq/ µmol), and serial dynamic scans were performed in the 3D data acquisition mode. The peak of the specific binding was not well defined with high SA due to the flatness of the curves after 60 min but was observed within the PET measurement. In the experiment with low SA, the peak came earlier than that with high SA. Scatchard analysis was performed using the maximal specific binding value (transient equilibrium) and the radioactivity in the cerebellum as free ligand concentration. The highest density was observed in the thalamus (2.3+/-0.6 pmol/ml), followed by the temporal cortex (1.5+/-0.5 pmol/ml), hippocampu...
Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease is a progressive dementia that is characterized by a loss of recent memory. Evidence has accumulated to support the hypothesis that synapses are critical storage sites for memory. However, it is still uncertain whether tau protein is involved in associative memory storage and whether tau is distributed in mature brain synapses. To address this question, we examined the synaptosomal distribution of tau protein in both JNPL3 transgenic mice expressing human P301L tau and non-transgenic littermates. The JNPL3 mouse line is known as one of the mouse models of human tauopathy that develop motor and behavioral deficits with intracellular tau aggregates in the spinal cord and brainstem. The phenotype of disease progression is highly dependent on strain background. In this study, we confirmed that male JNPL3 transgenic mice with C57BL/6J strain background showed neither any sign of motor deficits nor accumulation of hyperphosphorylated tau in the sarkosyl-insoluble fraction until 18 months of age. Subcellular fractionation analysis showed that both mouse tau and human P301L tau were present in the synaptosomal fraction. Those tau proteins were less-phosphorylated than tau in the cytosolic fraction. Human P301L tau was preferentially distributed in the synaptosomal fraction while mouse endogenous tau was more distributed in the cytosolic fraction. Interestingly, a human-specific tau band with phosphorylation at Ser199 and Ser396 was observed in the synaptosomal fraction of JNPL3 mice. This tau was not identical to either tau species in cytosolic fraction or a prominent hyperphosphorylated 64 kDa tau species that was altered to tau pathology. These results suggest that exogenous human P301L tau induces synaptosomal distribution of tau protein with a certain phosphorylation. Regulating the synaptosomal tau level might be a potential target for a therapeutic intervention directed at preventing neurodegeneration.
Vocalizations of common marmoset (Callithrix jacchus) were examined under experimental situations... more Vocalizations of common marmoset (Callithrix jacchus) were examined under experimental situations related to fear or anxiety. When marmosets were isolated in an unfamiliar environment, they frequently vocalized &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;tsik-egg&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; calls, which were the combination calls of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;tsik&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; followed by several &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;egg&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;. Tsik-egg calls were also observed after treatment with the anxiogenic drug FG-7142 (20mg/kg, sc). In contrast, when marmosets were exposed to predatory stimuli as fear-evoking situations, they frequently vocalized tsik solo calls as well as tsik-egg calls. These results suggest that marmosets dissociate the vocalization of tsik-egg and tsik calls under conditions related to fear/anxiety; tsik-egg solo vocalizations were emitted under anxiety-related conditions (e.g., isolation and anxiogenic drug treatment), whereas a mixed vocalization of tsik-egg and tsik was emitted when confronted with fear-provoking stimuli (i.e., threatening predatory stimuli). Tsik-egg call with/without tsik can be used as a specific vocal index of fear/anxiety in marmosets, which allows us to understand the neural mechanism of negative emotions in primate.
Dissociative amnesia is characterized by an inability to retrieve information already saved in me... more Dissociative amnesia is characterized by an inability to retrieve information already saved in memories. 5-HT has some role in neural regulatory control and may be related to the recovery from dissociative amnesia. To examine the role of 5-HT1A receptors in the recovery from dissociative amnesia, we performed two positron emission tomography (PET) scans on a 30-year-old patient of dissociative amnesia using [(11)C]WAY-100635, the first at amnesic state, and the second at the time he had recovered. Exploratory voxel-based analysis (VBA) was performed using SPM software. 5-HT1A BPND images were compared between the patient at amnesic and recovery states and healthy subjects (14 males, mean age 29.8 ± 6.45) with Jack-knife analysis. 5-HT1A receptor bindings of the patient at the recovery state were significantly higher than those of healthy subjects in the right superior and middle frontal cortex, left inferior frontal and orbitofrontal cortex and bilateral inferior temporal cortex. Th...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014
2-((1E,3E)-4-(6-((11)C-methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol ((11)C-PBB3)... more 2-((1E,3E)-4-(6-((11)C-methylamino)pyridin-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol ((11)C-PBB3) is a clinically useful PET probe that we developed for in vivo imaging of tau pathology in the human brain. To ensure the availability of this probe among multiple PET facilities, in the present study we established protocols for the radiosynthesis and quality control of (11)C-PBB3 and for the characterization of its photoisomerization, biodistribution, and metabolism. (11)C-PBB3 was synthesized by reaction of the tert-butyldimethylsilyl desmethyl precursor ( 1: ) with (11)C-methyl iodide using potassium hydroxide as a base, followed by deprotection. Photoisomerization of (11)C-PBB3 under fluorescent light was determined. The biodistribution and metabolite analysis of (11)C-PBB3 was determined in mice using the dissection method. (11)C-PBB3 was synthesized with 15.4% ± 2.8% radiochemical yield (decay-corrected, n = 50) based on the cyclotron-produced (11)C-CO2 and showed an averaged syn...
The discovery of tau mutations in frontotemporal dementia has been a key event in neurodegenerati... more The discovery of tau mutations in frontotemporal dementia has been a key event in neurodegenerative disease research. The rTg4510 mouse line expressing human tau with P301L FTDP-17-tau mutation has been established to understand the role of tau in neurodegeneration. Our histological analyses with tau antibodies and fluorescent tau ligands on rTg4510 mice revealed that tau oligomer formation was distinct from tangle formation. While in vivo imaging of mature tangles is now available, imaging biomarkers for tau oligomers would be useful for clarifying their roles in neurotoxicity and for diagnosing early-stage tau pathology.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
Noninvasive determination of amyloid-β peptide (Aβ) deposition has important significance for ear... more Noninvasive determination of amyloid-β peptide (Aβ) deposition has important significance for early diagnosis and medical intervention for Alzheimer's disease (AD). In the present study, we investigated the availability of radiolabeled DRM106 ((123/125)I-DRM106 [6-iodo-2-[4-(1H-3-pyrazolyl)phenyl]imidazo[1,2-a]pyridine]), a compound with sufficient affinity for the synthesis of human Aβ fibrils and satisfactory metabolic stability, as a SPECT ligand in living brains. The sensitivity of (125)I-DRM106 for detecting Aβ deposition was compared with that of (125)I-IMPY (2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), a well-known amyloid SPECT ligand, by ex vivo autoradiographic analyses in 18-mo-old amyloid precursor protein transgenic mice. To verify the sensitivity and quantitation of radiolabeled DRM106 for in vivo imaging, we compared the detectability of Aβ plaques with (123)I-DRM106 and a well-known amyloid PET agent, (11)C-labeled Pittsburgh compound B ((11)C-P...
Abstract: Earlier in vivo PET experiments have demonstrated the binding of the neuroprotective al... more Abstract: Earlier in vivo PET experiments have demonstrated the binding of the neuroprotective alkaloid vinpocetine to the peripheral benzodiazepine receptor (PBR) or, with other terminology, the TSPO (18kDa translocator protein). With the aim of ...
Dementia, a progressive cognitive decline, leads to a gradually increasing restriction of daily a... more Dementia, a progressive cognitive decline, leads to a gradually increasing restriction of daily activities. Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) is the most common form of dementia. The pathological features of AD include plaques and tangles which are constituted by amyloid beta peptide (A beta) and tau protein. These amyloidogenic molecules have been mechanistically implicated in the pathogenesis of AD and related neurodegenerative dementias. The key strategy for establishment of diagnostic and therapeutic approaches to AD is sensitive and specific detection of the incipient neuropathology characteristics of AD, combined with emerging treatments that counteract molecular processes in AD pathogenesis. Recent advances in molecular imaging research have enabled visualization of brain amyloidosis. The rapid development of different compounds suitable for visualizing amyloid would permit pathology-specific diagnosis of AD at an asymptomatic stage in a noninvasive manner, and could also allow early immunotherapeutic intervention without causing an excessive neuroinflammatory response.
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Papers by Tetsuya Suhara