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P.5.033 Imaging of microglial activation in patients with Alzheimer's disease using [C-11](R)-PK11195 PET
P5 Degenerative and neurological disorders and Disability Scale (DS) before and during a treatment with paroxetine (40mg/day). In particular, we evaluated the subjetcs on day 60, 120 and 180. Moreover, on these days we evaluated resting metabolic rate using Quark b2-stationary testing system (Cosmed, Rome) wich allows assessment of resting energy expenditure and respiratory quotient. 3. We used non-parametric statistics because of dimension o f the sample, in particular we used Wilcoxon tests to evaluate quantitative measures and Chisquare for dichotomous measures before and during a paroxetine treatment. We find a significant reduction o f PASS (p 0.05), FQ (p 0.01) and DS (p 0.01) scores during a treatment with paroxetine treatment. Moreover, the results showed a significant weight gain during a 6 months treatment with paroxetine in panic patients (p 0.02). We did not find any significant metabolic rate, whereas the results showed an increase of respiratory quotient during the paroxetine treatment (p 0.04). 4. This study presents some limitations. In particular, we cannot exclude a type II error related to the small size in the explanation of the absence o f the significant differences in the comparison o f metabolic rate before and during paroxetine treatement in this sample. The results seem to confirm both the clinically improvement and the weight gain in panic patients during o f paroxetine treatment. The results did not find a significant change of metabolic rate during a 6 months of paroxetine treatment, whereas the results showed a signifcant increse of respiratory quotient suggesting that the weight gain might be explaind by a main usage o f carbohydrate in the diet during a paroxetine treatment. If further studies with randomized, double-blind design and a larger sample will confirm the results of our preliminary work, then the results suggested the usage of a correct diet to control tha weight gain during a paroxetine treatment.
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binding by means of both Statistical Parametric Mapping (SPM) analysis and full kinetic analysis using a simplified reference tissue model and a plasma input model. Methods: 13 AD patients, fulfilling the N1NCDS-ADRDA criteria, and 17 age matched healthy controls have been included. Dynamic 3D PET scans, consisting o f 22 frames over 60 minutes, have been performed following a bolus injection o f [C-11](R)PK11195. During scanning arterial blood sampling, using an online detection system and manual sampling to generate a metabolite corrected arterial plasma input curve, was carried out. For each subject a Tl-weighted structural MRI scan was acquired. First, Va images using Logan plots and BP images using Ichise plots with the cerebellum as reference tissue input were generated. Both Va and BP images were used subsequently in SPM analyses to assess changes in PK11195 binding. Secondly, regions of interest (ROIs) were drawn on the individuals co-registered MRI scan. ROI were placed bilaterally in the posterior cingulate, medial temporal lobe, thalamus and cerebellum area. These ROI were projected onto the dynamic [C-11](R)-PK11195 scan to generate time-activity curves (TACs) for each region. These TACs were fitted using a) a simplified reference tissue model with the cerebellum as reference tissue [3] and b) a two tissue reversible plasma input model (K1/k2 ratio fixed to whole cortex). Results: SPM analyses based on Va images did not reveal any areas with any changes in PK11195 binding between both groups. SPM analysis based on BP images showed bilaterally slightly increased PK11195 binding (p 0.05) in the occipital and lateral temporal lobes of AD patients. ROI analysis using ANOVA with agea as covariate revealed no statistically significant differences in BO between groups, although with the two tissue reversible plasma input model a general trend for increased BP was found in patients with AD.
References [1] Bertani A, Perna G, Migliarese G, Di Pasquale D, Cucchi M, Caldirola D, Bellodi L, 2004. Comparison of the treatment with paroxetine and reboxetine in panic disorder: a randomized, single-blind study. Pharmacopsychiatry 37: 20(:~210. [2] Zimmermann U, Kraus T, Himmerich H, Schuld A, Pollmacher T, 2003. Epidemiology, implications and mechanism underlying drug-induced weight gain in psychiatric patients. Journal of psychiatric research 37: 193 220.
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Imaging of microglial activation in patients with Alzheimer's disease using [C-11](R)-PK11195 PET
A. Schuitemaker 1 *, B.N.M. Van Berckel 2, R. Boellaard 2, M.A. Kropholler2, C. Jonker3, D. J. Veltman4, R Scheltens5, A.A. Lammertsma2. j VU University Medical Centet; Nuclear
Medicine and P E T Research and Neurology, Amsterdam, The Netherlands; 2 VU University Medical Centet; Nuclear Medicine and P E T Research, The Netherlands; 3 VU University Medical Centet; Dep of Neurology and EMGO Institute, The Netherlands; 4 VU University Medical Centet; Nuclear Medicine and P E T resarch and Psychiatry, The Netherlands; 5 VU University Medical Centet; Department of Neurology, The Netherlands Background: The PET ligand [C-11](R)-PKll195 is a tracer to visualise in vivo microglial activation. Activated microglia has been shown to be present in neurodegenerative disorders, like Alzheimer's disease (AD). Two previous reports on P K l l 1 9 5 binding in AD provided contradictory results, showing differences in uptake [1,2]. In the present study we evaluated P K l l 1 9 5
Twotissuereversiblemodel Sit-nplified referencetissue model controls Patients P value controls Patients P value Post cingulate MTL Thalamus Cerebellum Cerebrum
1.39±0.29 1.71±0.86 0.18 1.62±0.33 1.85±0.78 0.27 1.46±0.411.69±0.63 0.27 1.41±0.25 1.58±0.63 0.35 1.59±0.231.92±0.74 0.11
0.038±0.040 0.053±0.048 0.41 0.083±0.044 0.073±0.070 0.57 0.024±0.053 0.020±0.036 0.62 0.055±0.0500.089±0.071 0.11
Conclusion: Overall, both SPM and ROI based analyses did not show increased [C-1 1](R)-PK1 1195 binding in AD, which is in accordance with the findings o f Groom et al. [2]. However, a trend of increased binding in the occipital and lateral temporal lobes was present in the SPM analysis based on BP images. This will be studied in more detail using full kinetic modelling and manual delineation of these and other brain structures.
References [1] Cagnin A, Brooks DJ et al., 2001. In-vivo measurement of activated microglia in dementia. Lancet 358, 461467. [2] Groom GN, Junk L e t al., 1995. PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer's disease. J Nucl Med 36, 2207 2210. [3] Lammertsma AA, Hume SP, 1996. Simplified reference tissue model for PET receptor studies. Neuroimage 4, 153 158.
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binding by means of both Statistical Parametric Mapping (SPM) analysis and full kinetic analysis using a simplified reference tissue model and a plasma input model. Methods: 13 AD patients, fulfilling the N1NCDS-ADRDA criteria, and 17 age matched healthy controls have been included. Dynamic 3D PET scans, consisting o f 22 frames over 60 minutes, have been performed following a bolus injection o f [C-11](R)PK11195. During scanning arterial blood sampling, using an online detection system and manual sampling to generate a metabolite corrected arterial plasma input curve, was carried out. For each subject a Tl-weighted structural MRI scan was acquired. First, Va images using Logan plots and BP images using Ichise plots with the cerebellum as reference tissue input were generated. Both Va and BP images were used subsequently in SPM analyses to assess changes in PK11195 binding. Secondly, regions of interest (ROIs) were drawn on the individuals co-registered MRI scan. ROI were placed bilaterally in the posterior cingulate, medial temporal lobe, thalamus and cerebellum area. These ROI were projected onto the dynamic [C-11](R)-PK11195 scan to generate time-activity curves (TACs) for each region. These TACs were fitted using a) a simplified reference tissue model with the cerebellum as reference tissue [3] and b) a two tissue reversible plasma input model (K1/k2 ratio fixed to whole cortex). Results: SPM analyses based on Va images did not reveal any areas with any changes in PK11195 binding between both groups. SPM analysis based on BP images showed bilaterally slightly increased PK11195 binding (p 0.05) in the occipital and lateral temporal lobes of AD patients. ROI analysis using ANOVA with agea as covariate revealed no statistically significant differences in BO between groups, although with the two tissue reversible plasma input model a general trend for increased BP was found in patients with AD.
References [1] Bertani A, Perna G, Migliarese G, Di Pasquale D, Cucchi M, Caldirola D, Bellodi L, 2004. Comparison of the treatment with paroxetine and reboxetine in panic disorder: a randomized, single-blind study. Pharmacopsychiatry 37: 20(:~210. [2] Zimmermann U, Kraus T, Himmerich H, Schuld A, Pollmacher T, 2003. Epidemiology, implications and mechanism underlying drug-induced weight gain in psychiatric patients. Journal of psychiatric research 37: 193 220.
•
Imaging of microglial activation in patients with Alzheimer's disease using [C-11](R)-PK11195 PET
A. Schuitemaker 1 *, B.N.M. Van Berckel 2, R. Boellaard 2, M.A. Kropholler2, C. Jonker3, D. J. Veltman4, R Scheltens5, A.A. Lammertsma2. j VU University Medical Centet; Nuclear
Medicine and P E T Research and Neurology, Amsterdam, The Netherlands; 2 VU University Medical Centet; Nuclear Medicine and P E T Research, The Netherlands; 3 VU University Medical Centet; Dep of Neurology and EMGO Institute, The Netherlands; 4 VU University Medical Centet; Nuclear Medicine and P E T resarch and Psychiatry, The Netherlands; 5 VU University Medical Centet; Department of Neurology, The Netherlands Background: The PET ligand [C-11](R)-PKll195 is a tracer to visualise in vivo microglial activation. Activated microglia has been shown to be present in neurodegenerative disorders, like Alzheimer's disease (AD). Two previous reports on P K l l 1 9 5 binding in AD provided contradictory results, showing differences in uptake [1,2]. In the present study we evaluated P K l l 1 9 5
Twotissuereversiblemodel Sit-nplified referencetissue model controls Patients P value controls Patients P value Post cingulate MTL Thalamus Cerebellum Cerebrum
1.39±0.29 1.71±0.86 0.18 1.62±0.33 1.85±0.78 0.27 1.46±0.411.69±0.63 0.27 1.41±0.25 1.58±0.63 0.35 1.59±0.231.92±0.74 0.11
0.038±0.040 0.053±0.048 0.41 0.083±0.044 0.073±0.070 0.57 0.024±0.053 0.020±0.036 0.62 0.055±0.0500.089±0.071 0.11
Conclusion: Overall, both SPM and ROI based analyses did not show increased [C-1 1](R)-PK1 1195 binding in AD, which is in accordance with the findings o f Groom et al. [2]. However, a trend of increased binding in the occipital and lateral temporal lobes was present in the SPM analysis based on BP images. This will be studied in more detail using full kinetic modelling and manual delineation of these and other brain structures.
References [1] Cagnin A, Brooks DJ et al., 2001. In-vivo measurement of activated microglia in dementia. Lancet 358, 461467. [2] Groom GN, Junk L e t al., 1995. PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer's disease. J Nucl Med 36, 2207 2210. [3] Lammertsma AA, Hume SP, 1996. Simplified reference tissue model for PET receptor studies. Neuroimage 4, 153 158.