373 research outputs found
Introduction on PET:Description of Basics and Principles
Full text linkPositron emission tomography (or PET) is a non-destructive imaging technique in nuclear medicine with several unique properties: high sensitivity, low radiation dose, possibility to correct data for attenuation and scatter (thus quantitative), radioactive labeling of natural substances or drugs with high specific radioactivities so that these can be used as tracers to monitor the pharmacokinetics of the non-radioactive compounds. Limitations are the spatial resolution of commercially available PET cameras, resulting in blurring or non-visibility of objects smaller than 1 mm, and the short half-lives of the commonly used PET radionuclides (< 2 h). Because of the combination of positron emitters, specific radiopharmaceuticals and quantitative data analysis, PET is frequently used to study the pharmacokinetics and pharmacodynamics of test drugs non-invasively in humans
Introduction on PET:Description of Basics and Principles
Full text linkPositron emission tomography (or PET) is a non-destructive imaging technique in nuclear medicine with several unique properties: high sensitivity, low radiation dose, possibility to correct data for attenuation and scatter (thus quantitative), radioactive labeling of natural substances or drugs with high specific radioactivities so that these can be used as tracers to monitor the pharmacokinetics of the non-radioactive compounds. Limitations are the spatial resolution of commercially available PET cameras, resulting in blurring or non-visibility of objects smaller than 1 mm, and the short half-lives of the commonly used PET radionuclides (< 2 h). Because of the combination of positron emitters, specific radiopharmaceuticals and quantitative data analysis, PET is frequently used to study the pharmacokinetics and pharmacodynamics of test drugs non-invasively in humans
Introduction on PET:Description of Basics and Principles
Full text linkPositron emission tomography (or PET) is a non-destructive imaging technique in nuclear medicine with several unique properties: high sensitivity, low radiation dose, possibility to correct data for attenuation and scatter (thus quantitative), radioactive labeling of natural substances or drugs with high specific radioactivities so that these can be used as tracers to monitor the pharmacokinetics of the non-radioactive compounds. Limitations are the spatial resolution of commercially available PET cameras, resulting in blurring or non-visibility of objects smaller than 1 mm, and the short half-lives of the commonly used PET radionuclides (< 2 h). Because of the combination of positron emitters, specific radiopharmaceuticals and quantitative data analysis, PET is frequently used to study the pharmacokinetics and pharmacodynamics of test drugs non-invasively in humans
Introduction on PET:Description of Basics and Principles
Full text linkPositron emission tomography (or PET) is a non-destructive imaging technique in nuclear medicine with several unique properties: high sensitivity, low radiation dose, possibility to correct data for attenuation and scatter (thus quantitative), radioactive labeling of natural substances or drugs with high specific radioactivities so that these can be used as tracers to monitor the pharmacokinetics of the non-radioactive compounds. Limitations are the spatial resolution of commercially available PET cameras, resulting in blurring or non-visibility of objects smaller than 1 mm, and the short half-lives of the commonly used PET radionuclides (< 2 h). Because of the combination of positron emitters, specific radiopharmaceuticals and quantitative data analysis, PET is frequently used to study the pharmacokinetics and pharmacodynamics of test drugs non-invasively in humans
Epilog
No full textIn this final chapter the contents of this book are briefly summarized. Some conclusions are drawn about the strengths and weaknesses of PET for use in drug development
Imaging Type I Glycine Transporters in the CNS using Positron Emission Tomography
No full text1. Type 1 glycine transporters in the human brain remain an attractive and relevant target for PET imaging. Schizophrenia is a severe mental disorder with a significant impact on life expectancy and a relatively high incidence (0.03– 0.07 % of global population). Partial inhibition of GlyT1 activity is proposed to improve cognitive impairment in schizophrenics. 2. In order to accurately understand the clinical relationship between the dose of a GlyT1 inhibitor and its effectiveness in cognitive models, an appropriate radioligand for use in PET or SPECT studies has to be available. There is thus an ongoing need for access to imaging tools which can be used in drug development and research focused on greater understanding of mechanisms underlying human disease. 3. Out of many currently reported radiopharmaceuticals for GlyT1, [ 11C] Ro5013853 appears to be the best suitable for determination of transporter occupancy by nonradioactive drugs. 4. Data from a range of tracers indicate that GlyT1 is expressed throughout the brain with no available reference region, resulting in high tracer binding in cerebellum, pons, thalamus and white matter of the frontal cortex, with lower tracer binding in putamen, caudate and cortical grey matter. 5. Many tracer candidates have not yet been fully characterised. For [ 18 F] MK6577, [ 11 C]-N-methyl-SSR5-4734 and [ 11 C]SA1, human data are missing. The specificity of [ 11 C]Ro5013853 for GlyT1 vs GlyT2 has not yet been examined. Further radiopharmaceutical development is necessary to improve on the existing choice
Positron Emission Tomography (PET) Imaging of Opioid Receptors
Full text linkThe opioid system consists of opioid receptors (which mediate the actions ofopium), their endogenous ligands (the enkephalins, endorphins, endomorphins,dynorphin, and nociceptin), and the proteins involved in opioid production,transport, and degradation. PET tracers for the various opioid receptor subtypesare available, and changes in regional opioidergic activity have been assessedduring both sensory and affective processing in healthy individuals and in various disease conditions such as chronic pain, neurodegeneration, epilepsy, eating disorders, behavioral addiction, and substance abuse. It is not always clear whether observed changes of tracer binding reflect altered release of endogenous opioids or altered opioid receptor expression. This issue may be resolved by studies in experimental animals that combine in vivo PET imaging with ex vivo immunohistochemistry. Some radioligands for opioid receptors have suboptimal kinetics (i.e., slow dissociation from their target protein) or can induce undesired side effects even at low administered doses (sedation, respiratory arrest). Yet, PET offers the unique opportunity of quantifying opioid receptor-mediated signaling in the living human brain. PET imaging has provided evidence for a link between opioid neurotransmission and peripheral immune activation
SPECT and PET in Eating Disorders
Full text linkMedical imaging techniques like PET and SPECT have been applied for investigation of brain function in anorexia and bulimia nervosa. Regional abnormalities have been detected in cerebral blood flow, glucose metabolism, the availability of several neurotransmitter receptors (serotonin 1A and 2A, dopamine D2/D3, histamine H1, mu-opioid, GABA(A)-benzodiazepine, and cannabinoid CB1), stimulant-induced dopamine release, presynaptic FDOPA influx, and the density of serotonin transporters. Different subtypes of eating disorders appear to be associated with specific functional changes. It is hard to judge whether such changes are a consequence of chronic dietary restrictions or are caused by a putative anorexia (or bulimia) nervosa endophenotype. Many abnormalities (particularly those of glucose metabolism) appear to be reversible after restoration of weight or normal patterns of food intake and may represent consequences of purging or starvation. However, some changes of regional flow and neurotransmitter systems persist even after successful therapy which suggests that these reflect traits that are independent of the state of the illness. Changes of the serotonergic system (altered activity of 5-HT1A and 5-HT2A receptors and 5-HT transporters) may contribute to dysregulation of appetite, mood, and impulse control in eating disorders and may represent a trait which predisposes to the development of anxiety, obsessionality, and behavioral inhibition. Assessment of functional changes in the brain with PET or SPECT may have prognostic value and predict neuropsychological status after several years of therapy
Epilog
No full textIn this final chapter the contents of this book are briefly summarized. Some conclusions are drawn about the strengths and weaknesses of PET for use in drug development
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