Alexandre Shoji | Irmandade da Santa Casa de Misericórdia de São Paulo (original) (raw)
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![Research paper thumbnail of PET Imaging with S-[11C]Methyl-L-Cysteine and L-[Methyl-11C]Methionine in Rat Models of Glioma, Glioma Radiotherapy, and Neuroinflammation](https://attachments.academia-assets.com/98431097/thumbnails/1.jpg)
](Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging, Jan 30, 2017
S-[11C]-methyl-L-cysteine ([11C]MCYS) has been claimed to offer higher tumor selectivity than L-[... more S-[11C]-methyl-L-cysteine ([11C]MCYS) has been claimed to offer higher tumor selectivity than L-[methyl- 11C]methionine ([11C]MET). We examined this claim in animal models. Rats with implanted untreated (n = 10) or irradiated (n = 7, 1 × 25 Gy, on day 8) orthotopic gliomas were scanned after 6, 9, and 12 days, using positron emission tomography. Rats with striatal injections of saline (n = 9) or bacterial lipopolysaccharide (n = 9) were scanned after 3 days. Uptake of the two tracers in untreated gliomas was similar. [11C]MCYS was not accumulated in salivary glands, nasal epithelium, and healing wounds, in contrast to [11C]MET, but showed 40 % higher accumulation in the healthy brain. Both tracers showed a reduced tumor uptake 4 days after irradiation and minor accumulation in inflamed striatum. [11C]MCYS indicated higher lesion volumes than [11C]MET (untreated tumor + 47 %; irradiated tumor up to + 500 %; LPS-inflamed striatum + 240 %). [11C]MCYS was less accumulated in some non-tu...
![Research paper thumbnail of EPA-1467 – Effects of treatment of schizophrenia on microglia: A [11C]PK11195 PET study](https://attachments.academia-assets.com/98431098/thumbnails/1.jpg)
](European Psychiatry, 2014
Molecular Imaging and Biology
Purpose Prenatal infection during pregnancy is a risk factor for schizophrenia, as well as for ot... more Purpose Prenatal infection during pregnancy is a risk factor for schizophrenia, as well as for other developmental psychiatric disorders, such as autism and bipolar disorder. Schizophrenia patients were reported to have altered brain metabolism and neuroinflammation. However, the link between prenatal infection, altered brain inflammation and metabolism, and schizophrenia remains unclear. In this project, we aimed to evaluate whether there are changes in brain glucose consumption and microglia activation in the offspring of pregnant rats exposed to maternal immune activation (MIA), and if so, whether these changes occur before or after the initiation of schizophrenia-like behaviour. Procedures Pregnant rats were treated with the viral mimic polyinosinic-polycytidylic acid (MIA group) or saline (control group) on gestational day 15. Static PET scans of the male offspring were acquired on postnatal day (PND) 21, 60, and 90, using [11C]-PK11195 and deoxy-2-[18F]fluoro-D-glucose ([18F]-...
European Journal of Nuclear Medicine and Molecular Imaging, 2014
![Research paper thumbnail of PET Imaging with S-[ 11 C]Methyl-L-Cysteine and L-[Methyl-11 C]Methionine in Rat Models of Glioma, Glioma Radiotherapy, and Neuroinflammation](https://attachments.academia-assets.com/72700057/thumbnails/1.jpg)
](Purpose: S-[ 11 C]-methyl-L-cysteine ([ 11 C]MCYS) has been claimed to offer higher tumor selecti... more Purpose: S-[ 11 C]-methyl-L-cysteine ([ 11 C]MCYS) has been claimed to offer higher tumor selectivity than L-[methyl-11 C]methionine ([ 11 C]MET). We examined this claim in animal models. Procedures: Rats with implanted untreated (n = 10) or irradiated (n = 7, 1 × 25 Gy, on day 8) orthotopic gliomas were scanned after 6, 9, and 12 days, using positron emission tomography. Rats with striatal injections of saline (n = 9) or bacterial lipopolysaccharide (n = 9) were scanned after 3 days. Results: Uptake of the two tracers in untreated gliomas was similar. [ 11 C]MCYS was not accumulated in salivary glands, nasal epithelium, and healing wounds, in contrast to [ 11 C]MET, but showed 40 % higher accumulation in the healthy brain. Both tracers showed a reduced tumor uptake 4 days after irradiation and minor accumulation in inflamed striatum. [ 11 C]MCYS indicated higher lesion volumes than [ 11 C]MET (untreated tumor + 47 %; irradiated tumor up to + 500 %; LPS-inflamed striatum + 240 %). C...
Nuclear Medicine and Biology, 2017
[(11)C]Flumazenil is a well-known PET tracer for GABAA receptors and is mainly used as an imaging... more [(11)C]Flumazenil is a well-known PET tracer for GABAA receptors and is mainly used as an imaging biomarker for neuronal loss. Recently, GABAA receptors on immune cells have been investigated as target for modulation of inflammation. Since neuronal loss is often accompanied by neuroinflammation, PET imaging with [(11)C]flumazenil is potentially affected by infiltrating immune cells. This may also compromise the validity of using the pons as reference tissue in quantitative pharmacokinetic analysis. This study aims to evaluate whether inflammatory processes in the brain can influence [(11)C]flumazenil uptake and affect the outcome of pharmacokinetic modeling when the pons is used as reference tissue. The herpes simplex encephalitis (HSE) rat model is known to cause neuroinflammation in the brainstem. Dynamic [(11)C]flumazenil PET scans of 60-min, accompanied by arterial blood sampling and metabolite analysis, were acquired at day 6-7days post-infection of male Wistar rats (HSE, n=5 and control, n=6). Additionally, the GABAA receptor was saturated by injection of unlabeled flumazenil prior to the tracer injection in 4 rats per group. PET data were analyzed by pharmacokinetic modeling. No statistically significant differences were found in the volume of distribution (VT) or non-displaceable binding potential (BPND) between control and HSE rats in any of the brain regions. Pre-saturation with unlabeled flumazenil resulted in a statistically significant reduction in [(11)C]flumazenil VT in all brain regions. The BPND obtained from SRTM exhibited a good correlation to DVR - 1 values from the two-tissue compartment model, coupled with some level of underestimation. Reliable quantification of [(11)C]flumazenil binding in rats can be obtained by pharmacokinetic analysis using the pons as a pseudo-reference tissue even in the presence of strong acute neuroinflammation.
Arquivos de neuro-psiquiatria, 2014
Neurology, Psychiatry and Brain Research, 2014
Epilepsia, 2003
The remarkable motor recovery observed after hemispherectomy in patients and experimental animals... more The remarkable motor recovery observed after hemispherectomy in patients and experimental animals has puzzled investigators, as it defies classic jacksonian neurology. Several mechanisms for this phenomenon have been considered, such as neuronal sprouting to subcortical structures, neurochemical changes, and cerebellar diaschisis. The spared hemisphere may, however, play a crucial part in this functional recovery. In this study, seven Wistar rats were submitted to right hemisphere motor area mapping. In the same anesthetic time, a left microsurgical hemispherectomy was performed, and the animal allowed to recover for 2 weeks. After then, the right hemisphere was again stimulated for its motor area. Four rats had, after 2 weeks of observation, bilateral body movements with stimulation of only the right hemisphere. The same segments on both sides had symmetric and simultaneous movements. The results suggest that each motor area has the latent capacity to control motricity bilaterally, and that such capacity is brought into function after removal of the opposite hemisphere. The same neuronal population that gives afference to one segment contralaterally seems to give afference to the same segment ipsilaterally.
![Research paper thumbnail of Contribution of neuroinflammation to changes in [11C]flumazenil binding in the rat brain: Evaluation of the inflamed pons as reference tissue](https://attachments.academia-assets.com/52397474/thumbnails/1.jpg)
](Introduction: [11C]Flumazenil is a well–known PET tracer for GABA A receptors and is mainly used ... more Introduction:
[11C]Flumazenil is a well–known PET tracer for GABA A receptors and is mainly used as an imaging biomarker for neuronal loss. Recently, GABA A receptors on immune cells have been investigated as target for modulation of inflammation. Since neuronal loss is often accompanied by neuroinflammation, PET imaging with [11C]flumazenil is potentially affected by infiltrating immune cells. This may also compromise the validity of using the pons as reference tissue in quantitative pharmacokinetic analysis. This study aims to evaluate whether inflammatory processes in the brain can influence [11C]flumazenil uptake and affect the outcome of pharmacokinetic modeling when the pons is used as reference tissue.
Methods:
The herpes simplex encephalitis (HSE) rat model is known to cause neuroinflammation in the brainstem. Dynamic [11C]flumazenil PET scans of 60-min, accompanied by arterial blood sampling and metabolite analysis, were acquired at day 6–7 days post-infection of male Wistar rats (HSE, n = 5 and control, n = 6). Additionally, the GABA A receptor was saturated by injection of unlabeled flumazenil prior to the tracer injection in 4 rats per group. PET data were analyzed by pharmacokinetic modeling.
Results:
No statistically significant differences were found in the volume of distribution (Vt) or non-displaceable binding potential (BPnd) between control and HSE rats in any of the brain regions. Pre-saturation with unlabeled flumazenil resulted in a statistically significant reduction in [11C]flumazenil Vt in all brain regions. The BPnd obtained from SRTM exhibited a good correlation to DVR – 1 values from the two-tissue compartment model, coupled with some level of underestimation.
Conclusion:
Reliable quantification of [11C]flumazenil binding in rats can be obtained by pharmacokinetic analysis using the pons as a pseudo-reference tissue even in the presence of strong acute neuroinflammation.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging, Jan 30, 2017
S-[11C]-methyl-L-cysteine ([11C]MCYS) has been claimed to offer higher tumor selectivity than L-[... more S-[11C]-methyl-L-cysteine ([11C]MCYS) has been claimed to offer higher tumor selectivity than L-[methyl- 11C]methionine ([11C]MET). We examined this claim in animal models. Rats with implanted untreated (n = 10) or irradiated (n = 7, 1 × 25 Gy, on day 8) orthotopic gliomas were scanned after 6, 9, and 12 days, using positron emission tomography. Rats with striatal injections of saline (n = 9) or bacterial lipopolysaccharide (n = 9) were scanned after 3 days. Uptake of the two tracers in untreated gliomas was similar. [11C]MCYS was not accumulated in salivary glands, nasal epithelium, and healing wounds, in contrast to [11C]MET, but showed 40 % higher accumulation in the healthy brain. Both tracers showed a reduced tumor uptake 4 days after irradiation and minor accumulation in inflamed striatum. [11C]MCYS indicated higher lesion volumes than [11C]MET (untreated tumor + 47 %; irradiated tumor up to + 500 %; LPS-inflamed striatum + 240 %). [11C]MCYS was less accumulated in some non-tu...
European Psychiatry, 2014
Molecular Imaging and Biology
Purpose Prenatal infection during pregnancy is a risk factor for schizophrenia, as well as for ot... more Purpose Prenatal infection during pregnancy is a risk factor for schizophrenia, as well as for other developmental psychiatric disorders, such as autism and bipolar disorder. Schizophrenia patients were reported to have altered brain metabolism and neuroinflammation. However, the link between prenatal infection, altered brain inflammation and metabolism, and schizophrenia remains unclear. In this project, we aimed to evaluate whether there are changes in brain glucose consumption and microglia activation in the offspring of pregnant rats exposed to maternal immune activation (MIA), and if so, whether these changes occur before or after the initiation of schizophrenia-like behaviour. Procedures Pregnant rats were treated with the viral mimic polyinosinic-polycytidylic acid (MIA group) or saline (control group) on gestational day 15. Static PET scans of the male offspring were acquired on postnatal day (PND) 21, 60, and 90, using [11C]-PK11195 and deoxy-2-[18F]fluoro-D-glucose ([18F]-...
European Journal of Nuclear Medicine and Molecular Imaging, 2014
Purpose: S-[ 11 C]-methyl-L-cysteine ([ 11 C]MCYS) has been claimed to offer higher tumor selecti... more Purpose: S-[ 11 C]-methyl-L-cysteine ([ 11 C]MCYS) has been claimed to offer higher tumor selectivity than L-[methyl-11 C]methionine ([ 11 C]MET). We examined this claim in animal models. Procedures: Rats with implanted untreated (n = 10) or irradiated (n = 7, 1 × 25 Gy, on day 8) orthotopic gliomas were scanned after 6, 9, and 12 days, using positron emission tomography. Rats with striatal injections of saline (n = 9) or bacterial lipopolysaccharide (n = 9) were scanned after 3 days. Results: Uptake of the two tracers in untreated gliomas was similar. [ 11 C]MCYS was not accumulated in salivary glands, nasal epithelium, and healing wounds, in contrast to [ 11 C]MET, but showed 40 % higher accumulation in the healthy brain. Both tracers showed a reduced tumor uptake 4 days after irradiation and minor accumulation in inflamed striatum. [ 11 C]MCYS indicated higher lesion volumes than [ 11 C]MET (untreated tumor + 47 %; irradiated tumor up to + 500 %; LPS-inflamed striatum + 240 %). C...
Nuclear Medicine and Biology, 2017
[(11)C]Flumazenil is a well-known PET tracer for GABAA receptors and is mainly used as an imaging... more [(11)C]Flumazenil is a well-known PET tracer for GABAA receptors and is mainly used as an imaging biomarker for neuronal loss. Recently, GABAA receptors on immune cells have been investigated as target for modulation of inflammation. Since neuronal loss is often accompanied by neuroinflammation, PET imaging with [(11)C]flumazenil is potentially affected by infiltrating immune cells. This may also compromise the validity of using the pons as reference tissue in quantitative pharmacokinetic analysis. This study aims to evaluate whether inflammatory processes in the brain can influence [(11)C]flumazenil uptake and affect the outcome of pharmacokinetic modeling when the pons is used as reference tissue. The herpes simplex encephalitis (HSE) rat model is known to cause neuroinflammation in the brainstem. Dynamic [(11)C]flumazenil PET scans of 60-min, accompanied by arterial blood sampling and metabolite analysis, were acquired at day 6-7days post-infection of male Wistar rats (HSE, n=5 and control, n=6). Additionally, the GABAA receptor was saturated by injection of unlabeled flumazenil prior to the tracer injection in 4 rats per group. PET data were analyzed by pharmacokinetic modeling. No statistically significant differences were found in the volume of distribution (VT) or non-displaceable binding potential (BPND) between control and HSE rats in any of the brain regions. Pre-saturation with unlabeled flumazenil resulted in a statistically significant reduction in [(11)C]flumazenil VT in all brain regions. The BPND obtained from SRTM exhibited a good correlation to DVR - 1 values from the two-tissue compartment model, coupled with some level of underestimation. Reliable quantification of [(11)C]flumazenil binding in rats can be obtained by pharmacokinetic analysis using the pons as a pseudo-reference tissue even in the presence of strong acute neuroinflammation.
Arquivos de neuro-psiquiatria, 2014
Neurology, Psychiatry and Brain Research, 2014
Epilepsia, 2003
The remarkable motor recovery observed after hemispherectomy in patients and experimental animals... more The remarkable motor recovery observed after hemispherectomy in patients and experimental animals has puzzled investigators, as it defies classic jacksonian neurology. Several mechanisms for this phenomenon have been considered, such as neuronal sprouting to subcortical structures, neurochemical changes, and cerebellar diaschisis. The spared hemisphere may, however, play a crucial part in this functional recovery. In this study, seven Wistar rats were submitted to right hemisphere motor area mapping. In the same anesthetic time, a left microsurgical hemispherectomy was performed, and the animal allowed to recover for 2 weeks. After then, the right hemisphere was again stimulated for its motor area. Four rats had, after 2 weeks of observation, bilateral body movements with stimulation of only the right hemisphere. The same segments on both sides had symmetric and simultaneous movements. The results suggest that each motor area has the latent capacity to control motricity bilaterally, and that such capacity is brought into function after removal of the opposite hemisphere. The same neuronal population that gives afference to one segment contralaterally seems to give afference to the same segment ipsilaterally.
Introduction: [11C]Flumazenil is a well–known PET tracer for GABA A receptors and is mainly used ... more Introduction:
[11C]Flumazenil is a well–known PET tracer for GABA A receptors and is mainly used as an imaging biomarker for neuronal loss. Recently, GABA A receptors on immune cells have been investigated as target for modulation of inflammation. Since neuronal loss is often accompanied by neuroinflammation, PET imaging with [11C]flumazenil is potentially affected by infiltrating immune cells. This may also compromise the validity of using the pons as reference tissue in quantitative pharmacokinetic analysis. This study aims to evaluate whether inflammatory processes in the brain can influence [11C]flumazenil uptake and affect the outcome of pharmacokinetic modeling when the pons is used as reference tissue.
Methods:
The herpes simplex encephalitis (HSE) rat model is known to cause neuroinflammation in the brainstem. Dynamic [11C]flumazenil PET scans of 60-min, accompanied by arterial blood sampling and metabolite analysis, were acquired at day 6–7 days post-infection of male Wistar rats (HSE, n = 5 and control, n = 6). Additionally, the GABA A receptor was saturated by injection of unlabeled flumazenil prior to the tracer injection in 4 rats per group. PET data were analyzed by pharmacokinetic modeling.
Results:
No statistically significant differences were found in the volume of distribution (Vt) or non-displaceable binding potential (BPnd) between control and HSE rats in any of the brain regions. Pre-saturation with unlabeled flumazenil resulted in a statistically significant reduction in [11C]flumazenil Vt in all brain regions. The BPnd obtained from SRTM exhibited a good correlation to DVR – 1 values from the two-tissue compartment model, coupled with some level of underestimation.
Conclusion:
Reliable quantification of [11C]flumazenil binding in rats can be obtained by pharmacokinetic analysis using the pons as a pseudo-reference tissue even in the presence of strong acute neuroinflammation.