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  • 1
    Online Resource
    Online Resource
    High-Affinity Dopamine D 2 /D 3 PET Radioligands 18 F-Fallypride and 11 C-FLB457: A Comparison of Kinetics in Extrastriatal Regions Using a Multiple-Injection Protocol
    SAGE Publications ; 2010
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 30, No. 5 ( 2010-05), p. 994-1007
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 30, No. 5 ( 2010-05), p. 994-1007
    Abstract: 18 F-Fallypride and 11 C-FLB457 are commonly used PET radioligands for imaging extrastriatal dopamine D 2 /D 3 receptors, but differences in their in vivo kinetics may affect the sensitivity for measuring subtle changes in receptor binding. Focusing on regions of low binding, a direct comparison of the kinetics of 18 F-fallypride and 11 C-FLB457 was made using a MI protocol. Injection protocols were designed to estimate K 1 , k 2 , f ND k on , B max , and k off in the midbrain and cortical regions of the rhesus monkey. 11 C-FLB457 cleared from the arterial plasma faster and yielded a ND space distribution volume ( K 1 / k 2 ) that is three times higher than 18 F-fallypride, primarily due to a slower k 2 (FAL:FLB; k 2 =0.54 min −1 :0.18 min −1 ). The dissociation rate constant, k off , was slower for 11 C-FLB457, resulting in a lower K Dapp than 18 F-fallypride (FAL:FLB; 0.39 nM:0.13 nM). Specific D 2 /D 3 binding could be detected in the cerebellum for 11 C-FLB457 but not 18 F-fallypride. Both radioligands can be used to image extrastriatal D 2 /D 3 receptors, with 11 C-FLB457 providing greater sensitivity to subtle changes in low-receptor-density cortical regions and 18 F-fallypride being more sensitive to endogenous dopamine displacement in medium-to-high-receptor-density regions. In the presence of specific D 2 /D 3 binding in the cerebellum, reference region analysis methods will give a greater bias in BP ND with 11 C-FLB457 than with 18 F-fallypride.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1038/jcbfm.2009.270
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
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  • 2
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    Online Resource
    Subthalamic Glutamic Acid Decarboxylase Gene Therapy: Changes in Motor Function and Cortical Metabolism
    SAGE Publications ; 2007
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 27, No. 3 ( 2007-03), p. 501-509
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 27, No. 3 ( 2007-03), p. 501-509
    Abstract: Parkinson's disease (PD) is associated with increased excitatory activity within the subthalamic nucleus (STN). We sought to inhibit STN output in hemiparkinsonian macaques by transfection with adeno-associated virus (AAV) containing the gene for glutamic acid decarboxylase (GAD). In total, 13 macaques were rendered hemiparkinsonian by right intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection. Seven animals were injected with AAV-GAD into the right STN, and six received an AAV gene for green fluorescent protein (GFP). Videotaped motor ratings were performed in a masked fashion on a weekly basis over a 55-week period. At 56 weeks, the animals were scanned with 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Histological examination was performed at the end of the study. No adverse events were observed after STN gene therapy. We found that the clinical rating scores for the two treatment groups had different patterns of change over time (group × time interaction, P 〈 0.001). On FDG PET, the GAD animals exhibited an increase in glucose utilization in the right motor cortex relative to GFP controls ( P 〈 0.001). Metabolism in this region correlated with clinical ratings at end point ( P 〈 0.01). Histology confirmed GAD expression in treated animals. These findings suggest that STN AAV-GAD is well tolerated and potentially effective in a primate model of PD. The changes in motor cortical glucose utilization observed after gene therapy are consistent with the modulation of metabolic brain networks associated with this disorder.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1038/sj.jcbfm.9600364
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2007
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  • 3
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    Online Resource
    Measurement of 5-HT 1A Receptor Density and in-vivo Binding Parameters of [ 18 F]mefway in the Nonhuman Primate
    SAGE Publications ; 2012
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 32, No. 8 ( 2012-08), p. 1546-1558
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 32, No. 8 ( 2012-08), p. 1546-1558
    Abstract: The goal of this work was to characterize the in-vivo behavior of [ 18 F]mefway as a suitable positron emission tomography (PET) radiotracer for the assay of 5-hydroxytryptamine 1A (5-HT 1A ) receptor density ( B max ). Six rhesus monkeys were studied using a multiple-injection (M-I) protocol consisting of three sequential bolus injections of [ 18 F]mefway. Injection times and amounts of unlabeled mefway were optimized for the precise measurement of B max and specific binding parameters k off and k on for estimation of apparent K D . The PET time series were acquired for 180 minutes with arterial sampling performed throughout. Compartmental analysis using the arterial input function was performed to obtain estimates for K 1 , k 2 , k off , B max , and K Dapp in the cerebral cortex and raphe nuclei (RN) using a model that accounted for nontracer doses of mefway. Averaged over subjects, highest binding was seen in the mesial temporal and dorsal anterior cingulate cortices with B max values of 42±8 and 36±8 pmol/mL, respectively, and lower values in the superior temporal cortex, RN, and parietal cortex of 24±4, 19±4, and 13±2 pmol/mL, respectively. The K Dapp of mefway for the 5-HT 1A receptor sites was 4.3±1.3 nmol/L. In conclusion, these results show that M-I [ 18 F]mefway PET experiments can be used for the in-vivo measurement of 5-HT 1A receptor density.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1038/jcbfm.2012.43
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
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