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2.022 EFFECT OF PRAMIPEXOLE ON REGIONAL CEREBRAL BLOOD FLOW IN PARKINSON'S DISEASE
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Tuesday, 13 December 2011 / Parkinsonism and Related Disorders 18S2 (2012) S81–S159
Results: The higher conconcordance between the clinic and the image diagnosis was in the early Parkinson disease and multisystem atrophy group. We also calculate the specifity and sensivity and positive and negative predictable valuable in diferenciate this two groups. Conclusions: 18FDG PET scan is a usefull tool to diferenciate Parkinson disease from multisistem atrophy in early stages of both diseases. This benefit has not been observed in the diferential diagnosis of other parkinsonian syndromes 2.020 SEMI-AUTOMATED SYNTHESIS, BIODISTRIBUTION AND MICROPET IMAGING OF 18 F-FP-DTBZ AS A VESICULAR MONOAMINE TRANSPORTER LIGAND Z. Chen, C. Liu, X. Li, J. Tang, C. Tan, H. Yu, H. Huang. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China Imaging vesicular monoamine transporter 2 (VMAT2) with positron emission tomography (PET) and radioligand has provided a noninvasive method for diagnosis and monitoring Parkionson Disease. This work was to develop a semi-automated synthesis of 18 FFP-DTBZ and validate its potential for VMAT2 imaging in rats. 18 F-FP-DTBZ was synthesized in a 20–30% yield without decay correction and with a radiochemical purity of >98%. Biodistribution studies in rats exhibited favorable brain uptake of the ligand (0.309±0.044ID% at 60 min post injection. mean±SD, n = 8). In the brain, highest radioactive concentration was observed in the striatum (ST, 0.672±0.119 ID%/g), whilst lowest concentration in the cerebellum (CB, 0.139±0.022ID%/g), giving the target-to-nontarget ratio (ST/CB) of 4.81±0.84. The striatum uptake could be blocked by DTBZ, a VMAT2 inhibitor, but not by CFT, a dopamine transporter inhibitor, suggesting its specificity to VMAT2. Rats microPET imaging with 18 F-FP-DTBZ gave high quality images in which clear 18 F-FP-DTBZ was found in the striatum symmetrically. Time-andactivity curves generated from region of interest (ROI) analysis revealed high 18 F-FP-DTBZ uptake and good retention in the target (striatum) and rapid clearance of radioactivity in the background (cerebellum), resulting in maximum ST/CB ratio value of 4.51±0.25 (mean±SD, n = 3, 80–120min). The 6-hydroxydopamine unilateral lesioned rats gave asymmetrical striata images with higher 18 F-FPDTBZ concentration on the unlesioned side (unlesioned-ST/CB = 3.86±0.98, n = 3) than the lesioned striatum (lesioned-ST/CB = 1.59±0.42, n = 3). The results reported here validated that 18 F-FPDTBZ is a favorable PET ligand binding to VMAT2 in rats. 2.021 DEMENTIA WITH LEWY BODIES CAN BE WELL-DIFFERENTIATED FROM ALZHEIMER’S DISEASE BY MEASUREMENT OF BRAIN ACETYLCHOLIN ESTERASE ACTIVITY BY PET H. Shimada1,2 , S. Hirano1,3 , H. Shinotoh1,4 , A. Aotsuka5 , K. Sato1 , N. Tanaka1 , T. Ota6 , M. Asahina3 , K. Fukushi7 , S. Kuwabara3 , T. Irie7 , H. Ito8 , T. Suhara1 . 1 Molecular Neuroimaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 2 Section for Human Neurophysiology, Research Center for Frontier Medical Engineering, Chiba University, Chiba, 3 Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, 4 Department of Neurology, Asahi Hospital for Neurological Disorders and Rehabilitation, Matsudo, 5 Department of Neurology, Chiba Aoba Municipal Hospital, Chiba, 6 Department of Psychiatry, Juntendo University, School of Medicine, Bunkyo, 7 Molecular Probe Program, Molecular Imaging Center, 8 Biophysics Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan Objective: The aim of our study was to investigate differential diagnostic performance by measuring brain acetylcholinesterase (AChE) activity using PET in patients with dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD).
Methods: Participants were 14 patients with DLB [age: 77±6 yrs, MMSE16±7], 25 patients with AD [age75±6 yrs, MMSE18±4] and 18 age-matched healthy controls [age: 72±9 yrs, MMSE30±1]. All subjects underwent PET scans with N-[11 C]-methyl-4-piperidyl acetate (MP4A) to measure regional brain AChE activity. We performed anatomical standardization of each brain image, and estimated k3 values, an index of AChE activity, in each voxels with a 2-tissue compatment 3-parameter model using the metabolite corrected arterial plasma input function. Volume of interest (VOIs) were identified on k3 images in frontal, temporal, parietal, and occipital cortices, and anterior and posterior cingulate gyrus (PCG) using the Wake Forest University Pick Atlas. The differential diagnostic performance was assessed by area under the receiver operating characteristic (ROC) curve analysis on k3 values in each VOIs between DLB and AD groups. Results: Cortical AChE activities were lower both in the DLB group (% reduction compared with the normal mean = −27.8%, p < 0.001) and in the AD group (−8.2%, p < 0.05) compared to the HC group. Most significant area under the ROC curves were observed in PCG (0.989, 95% CI, 0.926–0.999; sensitivity, 0.950; specificity, 0.943). Conclusions: PET measurement of brain AChE activity.may be useful for the differential diagnosis between DLB and AD. 2.022 EFFECT OF PRAMIPEXOLE ON REGIONAL CEREBRAL BLOOD FLOW IN PARKINSON’S DISEASE S. Hirano1,2 , H. Shinotoh1 , H. Shimada1 , M. Asahina2 , S. Kuwabara2 , D. Eidelberg3 , T. Suhara1 . 1 Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 2 Department of Neurology, Chiba School of Medicine, Chiba-shi, Japan; 3 Center for Neuroscience, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY, USA Objective: To assess the effects of pramipexole (nonergot dopamine agonist) on regional cerebral blood flow (rCBF) in resting-state Parkinson’s disease (PD) patients. Methods: Seven patients with de novo PD (age, 71.2 (6.3) years; Hoehn and Yahr stage, 2.3 (0.8) [mean (SD)] were participated. [99m Tc]-ethyl cysteinate dimer (ECD) SPECT were scanned twice. First scan was taken before the initiation of medication. Second scan was taken one hour after the morning dose of oral administration of pramipexole subsequent to two to three months of (daily dose 1.0 mg to 2.0 mg) pramipexole monotherapy. Statistical parametric mapping and network analysis (topographic profile rating) of PD cognitive pattern, characterized by covarying reduced metabolic activity in the prefrontal cortex and parietal association regions associated with relative increases in the dentate nuclei and cerebellar hemispheres, was used to identify significant rCBF changes by pramipexole. Height threshold value of p < 0.001 uncorrected and extent threshold <10 voxels was considered significant. Motor and neuropsychological function was assessment in each individual patient before each scan. Result: Pramipexole treatment improved UPDRS motor scores (UPDRS part III off 38.3 (11.3) -55.6%, p < 0.004) and phonemic verbal fluency (p < 0.03) in the patents. Regional CBF was significantly reduced in the left cerebellum, accompanied by increased rCBF in the left occipital lobe and the right frontal lobe (Brodmann’s area 10) during pramipexole treatment. PD cognitive pattern was reduced (improved) by the effect of pramipexole (p < 0.03). Conclusion: Pramipexole improves cognitive related brain network in patients with PD.
Tuesday, 13 December 2011 / Parkinsonism and Related Disorders 18S2 (2012) S81–S159
Results: The higher conconcordance between the clinic and the image diagnosis was in the early Parkinson disease and multisystem atrophy group. We also calculate the specifity and sensivity and positive and negative predictable valuable in diferenciate this two groups. Conclusions: 18FDG PET scan is a usefull tool to diferenciate Parkinson disease from multisistem atrophy in early stages of both diseases. This benefit has not been observed in the diferential diagnosis of other parkinsonian syndromes 2.020 SEMI-AUTOMATED SYNTHESIS, BIODISTRIBUTION AND MICROPET IMAGING OF 18 F-FP-DTBZ AS A VESICULAR MONOAMINE TRANSPORTER LIGAND Z. Chen, C. Liu, X. Li, J. Tang, C. Tan, H. Yu, H. Huang. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China Imaging vesicular monoamine transporter 2 (VMAT2) with positron emission tomography (PET) and radioligand has provided a noninvasive method for diagnosis and monitoring Parkionson Disease. This work was to develop a semi-automated synthesis of 18 FFP-DTBZ and validate its potential for VMAT2 imaging in rats. 18 F-FP-DTBZ was synthesized in a 20–30% yield without decay correction and with a radiochemical purity of >98%. Biodistribution studies in rats exhibited favorable brain uptake of the ligand (0.309±0.044ID% at 60 min post injection. mean±SD, n = 8). In the brain, highest radioactive concentration was observed in the striatum (ST, 0.672±0.119 ID%/g), whilst lowest concentration in the cerebellum (CB, 0.139±0.022ID%/g), giving the target-to-nontarget ratio (ST/CB) of 4.81±0.84. The striatum uptake could be blocked by DTBZ, a VMAT2 inhibitor, but not by CFT, a dopamine transporter inhibitor, suggesting its specificity to VMAT2. Rats microPET imaging with 18 F-FP-DTBZ gave high quality images in which clear 18 F-FP-DTBZ was found in the striatum symmetrically. Time-andactivity curves generated from region of interest (ROI) analysis revealed high 18 F-FP-DTBZ uptake and good retention in the target (striatum) and rapid clearance of radioactivity in the background (cerebellum), resulting in maximum ST/CB ratio value of 4.51±0.25 (mean±SD, n = 3, 80–120min). The 6-hydroxydopamine unilateral lesioned rats gave asymmetrical striata images with higher 18 F-FPDTBZ concentration on the unlesioned side (unlesioned-ST/CB = 3.86±0.98, n = 3) than the lesioned striatum (lesioned-ST/CB = 1.59±0.42, n = 3). The results reported here validated that 18 F-FPDTBZ is a favorable PET ligand binding to VMAT2 in rats. 2.021 DEMENTIA WITH LEWY BODIES CAN BE WELL-DIFFERENTIATED FROM ALZHEIMER’S DISEASE BY MEASUREMENT OF BRAIN ACETYLCHOLIN ESTERASE ACTIVITY BY PET H. Shimada1,2 , S. Hirano1,3 , H. Shinotoh1,4 , A. Aotsuka5 , K. Sato1 , N. Tanaka1 , T. Ota6 , M. Asahina3 , K. Fukushi7 , S. Kuwabara3 , T. Irie7 , H. Ito8 , T. Suhara1 . 1 Molecular Neuroimaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 2 Section for Human Neurophysiology, Research Center for Frontier Medical Engineering, Chiba University, Chiba, 3 Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, 4 Department of Neurology, Asahi Hospital for Neurological Disorders and Rehabilitation, Matsudo, 5 Department of Neurology, Chiba Aoba Municipal Hospital, Chiba, 6 Department of Psychiatry, Juntendo University, School of Medicine, Bunkyo, 7 Molecular Probe Program, Molecular Imaging Center, 8 Biophysics Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan Objective: The aim of our study was to investigate differential diagnostic performance by measuring brain acetylcholinesterase (AChE) activity using PET in patients with dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD).
Methods: Participants were 14 patients with DLB [age: 77±6 yrs, MMSE16±7], 25 patients with AD [age75±6 yrs, MMSE18±4] and 18 age-matched healthy controls [age: 72±9 yrs, MMSE30±1]. All subjects underwent PET scans with N-[11 C]-methyl-4-piperidyl acetate (MP4A) to measure regional brain AChE activity. We performed anatomical standardization of each brain image, and estimated k3 values, an index of AChE activity, in each voxels with a 2-tissue compatment 3-parameter model using the metabolite corrected arterial plasma input function. Volume of interest (VOIs) were identified on k3 images in frontal, temporal, parietal, and occipital cortices, and anterior and posterior cingulate gyrus (PCG) using the Wake Forest University Pick Atlas. The differential diagnostic performance was assessed by area under the receiver operating characteristic (ROC) curve analysis on k3 values in each VOIs between DLB and AD groups. Results: Cortical AChE activities were lower both in the DLB group (% reduction compared with the normal mean = −27.8%, p < 0.001) and in the AD group (−8.2%, p < 0.05) compared to the HC group. Most significant area under the ROC curves were observed in PCG (0.989, 95% CI, 0.926–0.999; sensitivity, 0.950; specificity, 0.943). Conclusions: PET measurement of brain AChE activity.may be useful for the differential diagnosis between DLB and AD. 2.022 EFFECT OF PRAMIPEXOLE ON REGIONAL CEREBRAL BLOOD FLOW IN PARKINSON’S DISEASE S. Hirano1,2 , H. Shinotoh1 , H. Shimada1 , M. Asahina2 , S. Kuwabara2 , D. Eidelberg3 , T. Suhara1 . 1 Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 2 Department of Neurology, Chiba School of Medicine, Chiba-shi, Japan; 3 Center for Neuroscience, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY, USA Objective: To assess the effects of pramipexole (nonergot dopamine agonist) on regional cerebral blood flow (rCBF) in resting-state Parkinson’s disease (PD) patients. Methods: Seven patients with de novo PD (age, 71.2 (6.3) years; Hoehn and Yahr stage, 2.3 (0.8) [mean (SD)] were participated. [99m Tc]-ethyl cysteinate dimer (ECD) SPECT were scanned twice. First scan was taken before the initiation of medication. Second scan was taken one hour after the morning dose of oral administration of pramipexole subsequent to two to three months of (daily dose 1.0 mg to 2.0 mg) pramipexole monotherapy. Statistical parametric mapping and network analysis (topographic profile rating) of PD cognitive pattern, characterized by covarying reduced metabolic activity in the prefrontal cortex and parietal association regions associated with relative increases in the dentate nuclei and cerebellar hemispheres, was used to identify significant rCBF changes by pramipexole. Height threshold value of p < 0.001 uncorrected and extent threshold <10 voxels was considered significant. Motor and neuropsychological function was assessment in each individual patient before each scan. Result: Pramipexole treatment improved UPDRS motor scores (UPDRS part III off 38.3 (11.3) -55.6%, p < 0.004) and phonemic verbal fluency (p < 0.03) in the patents. Regional CBF was significantly reduced in the left cerebellum, accompanied by increased rCBF in the left occipital lobe and the right frontal lobe (Brodmann’s area 10) during pramipexole treatment. PD cognitive pattern was reduced (improved) by the effect of pramipexole (p < 0.03). Conclusion: Pramipexole improves cognitive related brain network in patients with PD.