Jun Toyohara - Academia.edu (original) (raw)
Papers by Jun Toyohara
The Journal of Nuclear Medicine, 2012
EJNMMI Radiopharmacy and Chemistry, 2021
Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highligh... more Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to describe trends in the field. Results This commentary of highlights has resulted in 19 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Conclusion Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry.
European Journal of Nuclear Medicine and Molecular Imaging, 2021
Purpose 4′-[Methyl-11C] thiothymidine (4DST) incorporates into DNA directly and is a PET tracer u... more Purpose 4′-[Methyl-11C] thiothymidine (4DST) incorporates into DNA directly and is a PET tracer used for cell proliferation imaging. The aim of this study was to evaluate the prediction of prognosis with pretreatment 4DST PET/CT compared to fluorodeoxyglucose (FDG) PET/CT in patients with esophageal cancer. Methods In this prospective study, we analyzed 46 patients (68.2 ± 10.0 years old) with pathologically proven esophageal squamous cell cancer who underwent pretreatment 4DST and FDG PET/CT. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and total lesion proliferation (TLP) were measured for FDG and 4DST PET. The study endpoints were progression-free survival (PFS) and overall survival (OS). Patients’ clinical backgrounds, including age, histological type, clinical stage, and surgical treatment, were adjusted using the Cox proportional-hazards model. Results In the follow-up period (median 18.8 (interquartile range: 10.1–29.0) months), 26 and 19 patients showed disease progression and cancer-related death, respectively. After adjusting for clinical variables, only the 4DST parameters (SUVmax ( p = 0.001) and TLP ( p = 0.022)) were statistically significant for predicting PFS. FDG MTV ( p = 0.031), 4DST SUVmax ( p = 0.022), and TLP ( p = 0.023) were statistically significant for predicting OS. Of the PET parameters, 4DST SUVmax yielded the highest adjusted hazard ratio for both PFS (4.88, 95% confidence intervals (CI): 1.83–12.97) and OS (4.19, 95% CI: 1.23–14.20). Conclusion Higher accumulation of 4DST in the primary tumor may lead to shorter OS and PFS. 4DST PET/CT is useful for predicting prognosis and may outperform FDG PET/CT.
![Research paper thumbnail of Pharmacokinetic Modeling of [18F]MC225 for Quantification of the PGlycoprotein Function at the BloodBrain Barrier in Non-Human Primates with PET](https://attachments.academia-assets.com/94183900/thumbnails/1.jpg)
](MC225 has been developed as a weak substrate of P-glycoprotein (P-gp) aimed to measure changes in... more MC225 has been developed as a weak substrate of P-glycoprotein (P-gp) aimed to measure changes in the P-gp function at the blood−brain barrier with positron emission tomography. This study evaluates [ 18 F]MC225 kinetics in non-human primates and investigates the effect of both scan duration and P-gp inhibition. Three rhesus monkeys underwent two 91-min dynamic scans with blood sampling at baseline and after P-gp inhibition (8 mg/kg tariquidar). Data were analyzed using the 1-tissue compartment model (1-TCM) and 2-tissue compartment model (2-TCM) fits using metabolite-corrected plasma as the input function and for various scan durations (10, 20, 30, 60, and 91 min). The preferred model was chosen according to the Akaike information criterion and the standard errors (%) of the estimated parameters. For the 91-min scan duration, the influx constant K 1 increased by 40.7% and the volume of distribution (V T) by 30.4% after P-gp inhibition, while the efflux constant k 2 did not change significantly. Similar changes were found for all evaluated scan durations. K 1 did not depend on scan duration (10 minK 1 = 0.2191 vs 91 minK 1 = 0.2258), while V T and k 2 did. A scan duration of 10 min seems sufficient to properly evaluate the P-gp function using K 1 obtained with 1-TCM. For the 91-min scan, V T and K 1 can be estimated with a 2-TCM, and both parameters can be used to assess P-gp function.
Alzheimer's & Dementia, 2018
![Research paper thumbnail of A pitfall of white matter reference regions used in [18F] florbetapir PET: a consideration of kinetics](https://attachments.academia-assets.com/94183908/thumbnails/1.jpg)
](Annals of Nuclear Medicine, 2019
Objective Many studies have demonstrated the superiority of white matter (WM) reference regions (... more Objective Many studies have demonstrated the superiority of white matter (WM) reference regions (RR) in amyloid PET studies in comparison to cerebellar RR. However, the principle behind its improved measurement stability is yet to be elucidated. Our study aimed to determine the origin of WM stability; stability over cerebral blood flow and input function fluctuation or the greater statistical noise in the cerebellum due to its smaller size and its location in the axial periphery of the PET scanner bore. Methods We conducted simulations of [ 18 F] florbetapir using in-house program varying K 1 and input function, and adding statistical noise. Results Our simulations revealed that WM RR were more susceptible to CBF variation and input function fluctuation than cerebellar RR. WM RR did not gave superior measurement stability unless cerebellar statistical noise exceeded 4.55 times that in WM, a figure often surpassed in traditional amyloid PET studies. The greater statistical noise in cerebellum is likely the etiology for improved measurement stability of WM RR. Conclusion A longitudinal [ 18 F] florbetapir PET study should be conducted with a long bore PET. It can also be hypothesized that a second scan with the cerebellum in the axial center of a 3D PET, using a cerebellar RR to calculate changes in tracer concentration may improve the measurement stability of longitudinal [ 18 F] florbetapir studies.
Clinical nuclear medicine, 2017
A 41-year-old man underwent F-THK5351 PET 2 years after a right middle cerebral artery infarction... more A 41-year-old man underwent F-THK5351 PET 2 years after a right middle cerebral artery infarction. F-THK5351 PET imaging revealed intense radioligand uptake along the ipsilateral pyramidal tract from the corona radiata to the medulla; intense uptake changed from the right side to the left side with descending axial sections at the level of the pyramidal decussation. F-THK5351 reportedly binds to monoamine oxidase B, which is highly expressed in astrocytes, suggesting that F-THK5351 concentrates in the lesion where gliosis occurs. Hence, in this case, F-THK5351 uptake may represent Wallerian degeneration accompanied with gliosis in the ipsilateral pyramidal tract.
Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB), 2017
This study aimed to determine whether the SiPM-PET/CT, Discovery MI (DMI) performs better than th... more This study aimed to determine whether the SiPM-PET/CT, Discovery MI (DMI) performs better than the PMT-PET/CT system, Discovery 710 (D710). The physical performance of both systems was evaluated using NEMA NU 2 standards. Contrast (%), uniformity and image noise (%) are criteria proposed by the Japanese Society of Nuclear Medicine (JSNM) for phantom tests and were determined in images acquired from Hoffman and uniform phantoms using the DMI and D710. Brain and whole-body [F]FDG images were also acquired from a healthy male using the DMI and D710. The spatial resolution at 1.0cm off-center in the DMI and D710 was 3.91 and 4.52mm, respectively. The sensitivity of the DMI and D710 was 12.62 and 7.50cps/kBq, respectively. The observed peak noise-equivalent count rates were 185.6kcps at 22.5kBq/mL and 137.0kcps at 29.0kBq/mL, and the scatter fractions were 42.1% and 37.9% in the DMI and D710, respectively. The D710 had better contrast recovery and lower background variability. Contrast, ...
Frontiers in pharmacology, 2017
Adenosine Areceptors (ARs) are widely distributed throughout the entire human brain, while adenos... more Adenosine Areceptors (ARs) are widely distributed throughout the entire human brain, while adenosine Areceptors (ARs) are present in dopamine-rich areas of the brain, such as the basal ganglia. A past study using autoradiography reported a reduced binding ability of AR in the striatum of old rats. We developed positron emission tomography (PET) ligands for mapping the adenosine receptors and we successfully visualized the ARs using 8-dicyclopropylmethyl-1-C-methyl-3-propylxanthine (C-MPDX). We previously reported that the density of ARs decreased with age in the human striatum, although we could not observe an age-related change in ARs. The aim of this study was to investigate the age-related change of the density of ARs in the thalamus and cerebral cortices of healthy participants usingC-MPDX PET. We recruited eight young (22.0 ± 1.7 years) and nine elderly healthy male volunteers (65.7 ± 8.0 years). A dynamic series of decay-corrected PET scans was performed for 60 min starting wi...
International journal of sports medicine, Jan 22, 2018
Dynamic exercise elicits fluctuations in blood pressure (BP) and cerebral blood flow (CBF). This ... more Dynamic exercise elicits fluctuations in blood pressure (BP) and cerebral blood flow (CBF). This study investigated responses in BP and CBF during cycling exercise and post-exercise hypotension (PEH) using positron emission tomography (PET). CBF was measured using oxygen-15-labeled water (HO) and PET in 11 human subjects at rest (Rest), at the onset of exercise (Ex1), later in the exercise (Ex2), and during PEH. Global CBF significantly increased by 13% at Ex1 compared with Rest, but was unchanged at Ex2 and during PEH. Compared with at Rest, regional CBF (rCBF) increased at Ex1 (20~42%) in the cerebellar vermis, sensorimotor cortex for the bilateral legs (M1and S1), insular cortex and brain stem, but increased at Ex2 (28~31%) only in the vermis and M1and S1. During PEH, rCBF decreased compared with Rest (8~13%) in the cerebellum, temporal gyrus, piriform lobe, thalamus and pons. The areas showing correlations between rCBF and mean BP during exercise and PEH were consistent with the...
Journal of Neurotrauma, 2017
The positron emission tomography (PET) radioligand for adenosine A1 receptor (A1R) [1-methyl-11C]... more The positron emission tomography (PET) radioligand for adenosine A1 receptor (A1R) [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX) has recently been developed for human brain imaging. In the present study, we evaluated the alteration of the A1R in patients with diffuse axonal injury (DAI) in chronic stage in vivo. Ten patients with DAI (7 men and 3 women) were included in this study. Three PET examinations were sequentially performed to measure A1R binding with 11C-MPDX, glucose metabolism with 18F-fluorodeoxyglucose (FDG), and central benzodiazepine receptor binding with 11C-flumazenil (FMZ), and decreases of 11C-FMZ uptake indicate neuronal loss. 11C- MPDX did not depict any lesion with significantly decreased nondisplaceable binding potential (BPND) in comparison to healthy controls (14 men) in region of interest (ROI) analysis. Instead, it showed a significant increase of BPND in the lower frontal and posterior cingulate cortexes and rolandic area (p < 0.05) in ROI analysis. In 18F-FDG PET, the standardized uptake values (SUVs) ratio to the whole brain were decreased in anterior and posterior cingulate gyrus compared to controls (14 men and 9 women; p < 0.01). In 11C-FMZ PET, the SUV ratio to the cerebellum was decreased in anterior cingulate gyrus in ROI analysis (controls, 9 men and 6 women; p < 0.01). The area with significantly increased 11C-MPDX binding, lower frontal cortex, rolandic area, and posterior cingulate gyrus, did not overlap with the areas of neuronal loss detected by decreased 11C-FMZ binding and did not completely overlap with area of reduced18F-FDG uptake. We obtained the first 11C-MPDX PET images reflecting the A1R BPND in human DAI brain in vivo. 11C-MPDX depicted increased A1R BPND in the areas surrounding the injured brain, whereas 18F-FDG demonstrated reduction throughout the brain. The results suggested that A1R might continuously confer neuroprotective or neuromodulatory effects in DAI even in the chronic stage.
Current Pharmaceutical Design, 2016
Capillary endothelial cells in the brain express P-glycoprotein (P-gp), which works as a function... more Capillary endothelial cells in the brain express P-glycoprotein (P-gp), which works as a functional blood-brain barrier (BBB). P-gp pumps out multiple types of molecules from the brain parenchyma into the blood. Therefore, altered P-gp function at the BBB will change the concentrations of therapeutic drugs in the central nervous system (CNS) and hence impact the toxicity and efficacy of CNS drugs. Positron emission tomography (PET) is the only way to non-invasively measure P-gp function in the living human brain. PET imaging of P-gp function was first demonstrated in 1998 with the substrate tracer racemic [11C]verapamil. Since then, several drug interaction studies and proof-of-concept studies regarding drug resistance have been performed with P-gp PET imaging. Although preclinical findings have been very positive regarding the possibilities and importance of P-gp PET imaging, very few studies have shown the clinical relevance of P-gp PET imaging in different disorders of the brain. This review summarizes the pharmacological studies with PET using substrate tracers and emphasizes the importance of PET imaging to understand the mechanism of action of CNS drugs.
Cerebral Blood Flow and Metabolism (Japanese journal of cerebral blood flow and metabolism), 2017
PET imaging for altered brain function evoked by exercise: measurements of changes in cerebral bl... more PET imaging for altered brain function evoked by exercise: measurements of changes in cerebral blood flow and neurotransmitters
Radiological Physics and Technology, 2017
![Research paper thumbnail of Assessment of safety, efficacy, and dosimetry of a novel 18-kDa translocator protein ligand, [(11)C]CB184, in healthy human volunteers](https://attachments.academia-assets.com/94183854/thumbnails/1.jpg)
](EJNMMI research, 2017
N,N-di-n-propyl-2-[2-(4-[(11)C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ... more N,N-di-n-propyl-2-[2-(4-[(11)C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ([(11)C]CB184) is a novel selective radioligand for the 18-kD translocator protein (TSPO), which is upregulated in activated microglia in the brain, and may be useful in positron emission tomography (PET). We examined the safety, radiation dosimetry, and initial brain imaging with [(11)C]CB184 in healthy human volunteers. Dynamic [(11)C]CB184 PET scans (90 min) were performed in five healthy male subjects. During the scan, arterial blood was sampled at various time intervals, and the fraction of the parent compound in plasma was determined with high-performance liquid chromatography. No serious adverse events occurred in any of the subjects throughout the study period. [(11)C]CB184 was metabolized in the periphery: 36.7% ± 5.7% of the radioactivity in plasma was detected as the unchanged form after 60 min. The total distribution volume (V T) was estimated with a two-tissue compartment mo...
Neurobiology of aging, 2017
We examined possible age- and gender-related changes in binding of the selective antagonist N-[4-... more We examined possible age- and gender-related changes in binding of the selective antagonist N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-(11)C-methoxy-N-methylbenzamide ((11)C-ITMM) to metabotropic glutamate receptor type 1 in healthy human brains. Dynamic (11)C-ITMM positron emission tomography scans (90 min) with serial arterial blood sampling were performed in 15 young and 24 older healthy adult volunteers. The total distribution volume (VT) of several brain regions was estimated with 2-tissue compartment model analysis. The VTs of the cerebellar cortex, parietal cortex, putamen, amygdala, and hippocampus in older adult participants were significantly higher than in young participants. The age-related VT increase was only observed in male participants. Our data suggest that an age-dependent increase in metabotropic glutamate receptor type 1 availability in several brain regions may exist predominantly in males.
Internal medicine (Tokyo, Japan), 2017
The use of positron emission tomography (PET) imaging in progressive multifocal leukoencephalopat... more The use of positron emission tomography (PET) imaging in progressive multifocal leukoencephalopathy (PML) has rarely been reported. We herein report a set of PET images in a 63-year-old patient with PML. In PML lesions, the uptake of (18)F-fluorodeoxyglucose, (11)C-methionine, (11)C-flumazenil, and [methyl-(11)C]4'-thiothymidine was decreased, increased, decreased, and unchanged, respectively. These results suggest that glucose metabolism decreased, protein synthesis increased, neuronal integrity decreased, and the DNA synthesis and cellular proliferation of host cells were not activated in PML lesions. These results may reflect very little infiltration by inflammatory cells and active infection with JC virus in this case.
International journal of sports medicine, 2017
The central opioid receptor system likely contributes to the mechanism underlying the changes in ... more The central opioid receptor system likely contributes to the mechanism underlying the changes in affect elicited by exercise. Our aim was to use positron emission tomography (PET) to test whether exercise intensity influences activation of the μ-opioid receptor system in the brain, and whether changes in opioid receptor activation correlate with exercise-induced changes in affect. 7 healthy young male subjects (23±2 years) performed 20-min constant-load cycling exercises at heavy (ExH) and severe-intensity (ExS), and PET was performed using [(11)C]carfentanil as a tracer before and after each exercise. Exercise elicited the μ-opioidergic system activation in the large areas of the limbic system, particularly in the insular cortex, and cerebellum. Of note, deactivation of the μ-opioidergic system in the pituitary gland was identified as a specific finding in ExS, which evoked a distinctive sensation of fatigue. Within these brain areas, μ-opioid receptor activation correlated positiv...
Annals of Nuclear Medicine, 2016
Objective To elucidate the radionuclides and radiochemical impurities included in radiosynthesis ... more Objective To elucidate the radionuclides and radiochemical impurities included in radiosynthesis processes of positron emission tomography (PET) tracers. Methods Target materials and PET tracers were produced using a cyclotron/synthesis system from Sumitomo Heavy Industry. Positron and c-ray emitting radionuclides were quantified by measuring radioactivity decay and using the high-purity Ge detector, respectively. Radiochemical species in gaseous and aqueous target materials were analyzed by gas and ion chromatography, respectively. Results Target materials had considerable levels of several positron emitters in addition to the positron of interest, and in the case of aqueous target materials extremely low levels of many c-emitters. Five 11 C-, 15 O-, or 18 F-labeled tracers produced from gaseous materials via chemical reactions had no radionuclidic impurities, whereas 18 F-FDG, 18 F-NaF, and 13 N-NH 3 produced from aqueous materials had several c-emitters as well as impure positron emitters. 15 O-Labeled CO 2 , O 2 , and CO had a radionuclidic impurity 13 N-N 2 (0.5-0.7 %). Conclusions Target materials had several positron emitters other than the positron of interest, and extremely low level c-emitters in the case of aqueous materials. PET tracers produced from gaseous materials except for 15 O-labeled gases had no impure radionuclides, whereas those derived from aqueous materials contained acceptable levels of impure positron emitters and extremely low levels of several c-emitters.
Journal of Neurology, 2016
The Journal of Nuclear Medicine, 2012
EJNMMI Radiopharmacy and Chemistry, 2021
Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highligh... more Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to describe trends in the field. Results This commentary of highlights has resulted in 19 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Conclusion Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry.
European Journal of Nuclear Medicine and Molecular Imaging, 2021
Purpose 4′-[Methyl-11C] thiothymidine (4DST) incorporates into DNA directly and is a PET tracer u... more Purpose 4′-[Methyl-11C] thiothymidine (4DST) incorporates into DNA directly and is a PET tracer used for cell proliferation imaging. The aim of this study was to evaluate the prediction of prognosis with pretreatment 4DST PET/CT compared to fluorodeoxyglucose (FDG) PET/CT in patients with esophageal cancer. Methods In this prospective study, we analyzed 46 patients (68.2 ± 10.0 years old) with pathologically proven esophageal squamous cell cancer who underwent pretreatment 4DST and FDG PET/CT. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and total lesion proliferation (TLP) were measured for FDG and 4DST PET. The study endpoints were progression-free survival (PFS) and overall survival (OS). Patients’ clinical backgrounds, including age, histological type, clinical stage, and surgical treatment, were adjusted using the Cox proportional-hazards model. Results In the follow-up period (median 18.8 (interquartile range: 10.1–29.0) months), 26 and 19 patients showed disease progression and cancer-related death, respectively. After adjusting for clinical variables, only the 4DST parameters (SUVmax ( p = 0.001) and TLP ( p = 0.022)) were statistically significant for predicting PFS. FDG MTV ( p = 0.031), 4DST SUVmax ( p = 0.022), and TLP ( p = 0.023) were statistically significant for predicting OS. Of the PET parameters, 4DST SUVmax yielded the highest adjusted hazard ratio for both PFS (4.88, 95% confidence intervals (CI): 1.83–12.97) and OS (4.19, 95% CI: 1.23–14.20). Conclusion Higher accumulation of 4DST in the primary tumor may lead to shorter OS and PFS. 4DST PET/CT is useful for predicting prognosis and may outperform FDG PET/CT.
MC225 has been developed as a weak substrate of P-glycoprotein (P-gp) aimed to measure changes in... more MC225 has been developed as a weak substrate of P-glycoprotein (P-gp) aimed to measure changes in the P-gp function at the blood−brain barrier with positron emission tomography. This study evaluates [ 18 F]MC225 kinetics in non-human primates and investigates the effect of both scan duration and P-gp inhibition. Three rhesus monkeys underwent two 91-min dynamic scans with blood sampling at baseline and after P-gp inhibition (8 mg/kg tariquidar). Data were analyzed using the 1-tissue compartment model (1-TCM) and 2-tissue compartment model (2-TCM) fits using metabolite-corrected plasma as the input function and for various scan durations (10, 20, 30, 60, and 91 min). The preferred model was chosen according to the Akaike information criterion and the standard errors (%) of the estimated parameters. For the 91-min scan duration, the influx constant K 1 increased by 40.7% and the volume of distribution (V T) by 30.4% after P-gp inhibition, while the efflux constant k 2 did not change significantly. Similar changes were found for all evaluated scan durations. K 1 did not depend on scan duration (10 minK 1 = 0.2191 vs 91 minK 1 = 0.2258), while V T and k 2 did. A scan duration of 10 min seems sufficient to properly evaluate the P-gp function using K 1 obtained with 1-TCM. For the 91-min scan, V T and K 1 can be estimated with a 2-TCM, and both parameters can be used to assess P-gp function.
Alzheimer's & Dementia, 2018
Annals of Nuclear Medicine, 2019
Objective Many studies have demonstrated the superiority of white matter (WM) reference regions (... more Objective Many studies have demonstrated the superiority of white matter (WM) reference regions (RR) in amyloid PET studies in comparison to cerebellar RR. However, the principle behind its improved measurement stability is yet to be elucidated. Our study aimed to determine the origin of WM stability; stability over cerebral blood flow and input function fluctuation or the greater statistical noise in the cerebellum due to its smaller size and its location in the axial periphery of the PET scanner bore. Methods We conducted simulations of [ 18 F] florbetapir using in-house program varying K 1 and input function, and adding statistical noise. Results Our simulations revealed that WM RR were more susceptible to CBF variation and input function fluctuation than cerebellar RR. WM RR did not gave superior measurement stability unless cerebellar statistical noise exceeded 4.55 times that in WM, a figure often surpassed in traditional amyloid PET studies. The greater statistical noise in cerebellum is likely the etiology for improved measurement stability of WM RR. Conclusion A longitudinal [ 18 F] florbetapir PET study should be conducted with a long bore PET. It can also be hypothesized that a second scan with the cerebellum in the axial center of a 3D PET, using a cerebellar RR to calculate changes in tracer concentration may improve the measurement stability of longitudinal [ 18 F] florbetapir studies.
Clinical nuclear medicine, 2017
A 41-year-old man underwent F-THK5351 PET 2 years after a right middle cerebral artery infarction... more A 41-year-old man underwent F-THK5351 PET 2 years after a right middle cerebral artery infarction. F-THK5351 PET imaging revealed intense radioligand uptake along the ipsilateral pyramidal tract from the corona radiata to the medulla; intense uptake changed from the right side to the left side with descending axial sections at the level of the pyramidal decussation. F-THK5351 reportedly binds to monoamine oxidase B, which is highly expressed in astrocytes, suggesting that F-THK5351 concentrates in the lesion where gliosis occurs. Hence, in this case, F-THK5351 uptake may represent Wallerian degeneration accompanied with gliosis in the ipsilateral pyramidal tract.
Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB), 2017
This study aimed to determine whether the SiPM-PET/CT, Discovery MI (DMI) performs better than th... more This study aimed to determine whether the SiPM-PET/CT, Discovery MI (DMI) performs better than the PMT-PET/CT system, Discovery 710 (D710). The physical performance of both systems was evaluated using NEMA NU 2 standards. Contrast (%), uniformity and image noise (%) are criteria proposed by the Japanese Society of Nuclear Medicine (JSNM) for phantom tests and were determined in images acquired from Hoffman and uniform phantoms using the DMI and D710. Brain and whole-body [F]FDG images were also acquired from a healthy male using the DMI and D710. The spatial resolution at 1.0cm off-center in the DMI and D710 was 3.91 and 4.52mm, respectively. The sensitivity of the DMI and D710 was 12.62 and 7.50cps/kBq, respectively. The observed peak noise-equivalent count rates were 185.6kcps at 22.5kBq/mL and 137.0kcps at 29.0kBq/mL, and the scatter fractions were 42.1% and 37.9% in the DMI and D710, respectively. The D710 had better contrast recovery and lower background variability. Contrast, ...
Frontiers in pharmacology, 2017
Adenosine Areceptors (ARs) are widely distributed throughout the entire human brain, while adenos... more Adenosine Areceptors (ARs) are widely distributed throughout the entire human brain, while adenosine Areceptors (ARs) are present in dopamine-rich areas of the brain, such as the basal ganglia. A past study using autoradiography reported a reduced binding ability of AR in the striatum of old rats. We developed positron emission tomography (PET) ligands for mapping the adenosine receptors and we successfully visualized the ARs using 8-dicyclopropylmethyl-1-C-methyl-3-propylxanthine (C-MPDX). We previously reported that the density of ARs decreased with age in the human striatum, although we could not observe an age-related change in ARs. The aim of this study was to investigate the age-related change of the density of ARs in the thalamus and cerebral cortices of healthy participants usingC-MPDX PET. We recruited eight young (22.0 ± 1.7 years) and nine elderly healthy male volunteers (65.7 ± 8.0 years). A dynamic series of decay-corrected PET scans was performed for 60 min starting wi...
International journal of sports medicine, Jan 22, 2018
Dynamic exercise elicits fluctuations in blood pressure (BP) and cerebral blood flow (CBF). This ... more Dynamic exercise elicits fluctuations in blood pressure (BP) and cerebral blood flow (CBF). This study investigated responses in BP and CBF during cycling exercise and post-exercise hypotension (PEH) using positron emission tomography (PET). CBF was measured using oxygen-15-labeled water (HO) and PET in 11 human subjects at rest (Rest), at the onset of exercise (Ex1), later in the exercise (Ex2), and during PEH. Global CBF significantly increased by 13% at Ex1 compared with Rest, but was unchanged at Ex2 and during PEH. Compared with at Rest, regional CBF (rCBF) increased at Ex1 (20~42%) in the cerebellar vermis, sensorimotor cortex for the bilateral legs (M1and S1), insular cortex and brain stem, but increased at Ex2 (28~31%) only in the vermis and M1and S1. During PEH, rCBF decreased compared with Rest (8~13%) in the cerebellum, temporal gyrus, piriform lobe, thalamus and pons. The areas showing correlations between rCBF and mean BP during exercise and PEH were consistent with the...
Journal of Neurotrauma, 2017
The positron emission tomography (PET) radioligand for adenosine A1 receptor (A1R) [1-methyl-11C]... more The positron emission tomography (PET) radioligand for adenosine A1 receptor (A1R) [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX) has recently been developed for human brain imaging. In the present study, we evaluated the alteration of the A1R in patients with diffuse axonal injury (DAI) in chronic stage in vivo. Ten patients with DAI (7 men and 3 women) were included in this study. Three PET examinations were sequentially performed to measure A1R binding with 11C-MPDX, glucose metabolism with 18F-fluorodeoxyglucose (FDG), and central benzodiazepine receptor binding with 11C-flumazenil (FMZ), and decreases of 11C-FMZ uptake indicate neuronal loss. 11C- MPDX did not depict any lesion with significantly decreased nondisplaceable binding potential (BPND) in comparison to healthy controls (14 men) in region of interest (ROI) analysis. Instead, it showed a significant increase of BPND in the lower frontal and posterior cingulate cortexes and rolandic area (p < 0.05) in ROI analysis. In 18F-FDG PET, the standardized uptake values (SUVs) ratio to the whole brain were decreased in anterior and posterior cingulate gyrus compared to controls (14 men and 9 women; p < 0.01). In 11C-FMZ PET, the SUV ratio to the cerebellum was decreased in anterior cingulate gyrus in ROI analysis (controls, 9 men and 6 women; p < 0.01). The area with significantly increased 11C-MPDX binding, lower frontal cortex, rolandic area, and posterior cingulate gyrus, did not overlap with the areas of neuronal loss detected by decreased 11C-FMZ binding and did not completely overlap with area of reduced18F-FDG uptake. We obtained the first 11C-MPDX PET images reflecting the A1R BPND in human DAI brain in vivo. 11C-MPDX depicted increased A1R BPND in the areas surrounding the injured brain, whereas 18F-FDG demonstrated reduction throughout the brain. The results suggested that A1R might continuously confer neuroprotective or neuromodulatory effects in DAI even in the chronic stage.
Current Pharmaceutical Design, 2016
Capillary endothelial cells in the brain express P-glycoprotein (P-gp), which works as a function... more Capillary endothelial cells in the brain express P-glycoprotein (P-gp), which works as a functional blood-brain barrier (BBB). P-gp pumps out multiple types of molecules from the brain parenchyma into the blood. Therefore, altered P-gp function at the BBB will change the concentrations of therapeutic drugs in the central nervous system (CNS) and hence impact the toxicity and efficacy of CNS drugs. Positron emission tomography (PET) is the only way to non-invasively measure P-gp function in the living human brain. PET imaging of P-gp function was first demonstrated in 1998 with the substrate tracer racemic [11C]verapamil. Since then, several drug interaction studies and proof-of-concept studies regarding drug resistance have been performed with P-gp PET imaging. Although preclinical findings have been very positive regarding the possibilities and importance of P-gp PET imaging, very few studies have shown the clinical relevance of P-gp PET imaging in different disorders of the brain. This review summarizes the pharmacological studies with PET using substrate tracers and emphasizes the importance of PET imaging to understand the mechanism of action of CNS drugs.
Cerebral Blood Flow and Metabolism (Japanese journal of cerebral blood flow and metabolism), 2017
PET imaging for altered brain function evoked by exercise: measurements of changes in cerebral bl... more PET imaging for altered brain function evoked by exercise: measurements of changes in cerebral blood flow and neurotransmitters
Radiological Physics and Technology, 2017
EJNMMI research, 2017
N,N-di-n-propyl-2-[2-(4-[(11)C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ... more N,N-di-n-propyl-2-[2-(4-[(11)C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ([(11)C]CB184) is a novel selective radioligand for the 18-kD translocator protein (TSPO), which is upregulated in activated microglia in the brain, and may be useful in positron emission tomography (PET). We examined the safety, radiation dosimetry, and initial brain imaging with [(11)C]CB184 in healthy human volunteers. Dynamic [(11)C]CB184 PET scans (90 min) were performed in five healthy male subjects. During the scan, arterial blood was sampled at various time intervals, and the fraction of the parent compound in plasma was determined with high-performance liquid chromatography. No serious adverse events occurred in any of the subjects throughout the study period. [(11)C]CB184 was metabolized in the periphery: 36.7% ± 5.7% of the radioactivity in plasma was detected as the unchanged form after 60 min. The total distribution volume (V T) was estimated with a two-tissue compartment mo...
Neurobiology of aging, 2017
We examined possible age- and gender-related changes in binding of the selective antagonist N-[4-... more We examined possible age- and gender-related changes in binding of the selective antagonist N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-(11)C-methoxy-N-methylbenzamide ((11)C-ITMM) to metabotropic glutamate receptor type 1 in healthy human brains. Dynamic (11)C-ITMM positron emission tomography scans (90 min) with serial arterial blood sampling were performed in 15 young and 24 older healthy adult volunteers. The total distribution volume (VT) of several brain regions was estimated with 2-tissue compartment model analysis. The VTs of the cerebellar cortex, parietal cortex, putamen, amygdala, and hippocampus in older adult participants were significantly higher than in young participants. The age-related VT increase was only observed in male participants. Our data suggest that an age-dependent increase in metabotropic glutamate receptor type 1 availability in several brain regions may exist predominantly in males.
Internal medicine (Tokyo, Japan), 2017
The use of positron emission tomography (PET) imaging in progressive multifocal leukoencephalopat... more The use of positron emission tomography (PET) imaging in progressive multifocal leukoencephalopathy (PML) has rarely been reported. We herein report a set of PET images in a 63-year-old patient with PML. In PML lesions, the uptake of (18)F-fluorodeoxyglucose, (11)C-methionine, (11)C-flumazenil, and [methyl-(11)C]4'-thiothymidine was decreased, increased, decreased, and unchanged, respectively. These results suggest that glucose metabolism decreased, protein synthesis increased, neuronal integrity decreased, and the DNA synthesis and cellular proliferation of host cells were not activated in PML lesions. These results may reflect very little infiltration by inflammatory cells and active infection with JC virus in this case.
International journal of sports medicine, 2017
The central opioid receptor system likely contributes to the mechanism underlying the changes in ... more The central opioid receptor system likely contributes to the mechanism underlying the changes in affect elicited by exercise. Our aim was to use positron emission tomography (PET) to test whether exercise intensity influences activation of the μ-opioid receptor system in the brain, and whether changes in opioid receptor activation correlate with exercise-induced changes in affect. 7 healthy young male subjects (23±2 years) performed 20-min constant-load cycling exercises at heavy (ExH) and severe-intensity (ExS), and PET was performed using [(11)C]carfentanil as a tracer before and after each exercise. Exercise elicited the μ-opioidergic system activation in the large areas of the limbic system, particularly in the insular cortex, and cerebellum. Of note, deactivation of the μ-opioidergic system in the pituitary gland was identified as a specific finding in ExS, which evoked a distinctive sensation of fatigue. Within these brain areas, μ-opioid receptor activation correlated positiv...
Annals of Nuclear Medicine, 2016
Objective To elucidate the radionuclides and radiochemical impurities included in radiosynthesis ... more Objective To elucidate the radionuclides and radiochemical impurities included in radiosynthesis processes of positron emission tomography (PET) tracers. Methods Target materials and PET tracers were produced using a cyclotron/synthesis system from Sumitomo Heavy Industry. Positron and c-ray emitting radionuclides were quantified by measuring radioactivity decay and using the high-purity Ge detector, respectively. Radiochemical species in gaseous and aqueous target materials were analyzed by gas and ion chromatography, respectively. Results Target materials had considerable levels of several positron emitters in addition to the positron of interest, and in the case of aqueous target materials extremely low levels of many c-emitters. Five 11 C-, 15 O-, or 18 F-labeled tracers produced from gaseous materials via chemical reactions had no radionuclidic impurities, whereas 18 F-FDG, 18 F-NaF, and 13 N-NH 3 produced from aqueous materials had several c-emitters as well as impure positron emitters. 15 O-Labeled CO 2 , O 2 , and CO had a radionuclidic impurity 13 N-N 2 (0.5-0.7 %). Conclusions Target materials had several positron emitters other than the positron of interest, and extremely low level c-emitters in the case of aqueous materials. PET tracers produced from gaseous materials except for 15 O-labeled gases had no impure radionuclides, whereas those derived from aqueous materials contained acceptable levels of impure positron emitters and extremely low levels of several c-emitters.
Journal of Neurology, 2016