scholarly journals [18F]altanserin Binding to Human 5HT2A Receptors is Unaltered after Citalopram and Pindolol Challenge

2004 ◽  
Vol 24 (9) ◽  
pp. 1037-1045 ◽  
Author(s):  
Lars H. Pinborg ◽  
Karen H. Adams ◽  
Stig Yndgaard ◽  
Steen G. Hasselbalch ◽  
Søren Holm ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Constant Infusion ◽  
Plasma Prolactin ◽  
Hot Flushes ◽  
Experimental Paradigm ◽  
Pronounced Increase ◽  
Cellular Events ◽  
Positron Emission

The aim of the present study was to develop an experimental paradigm for the study of serotonergic neurotransmission in humans using positron emission tomography and the 5-HT2A selective radioligand [18F]altanserin. [18F]altanserin studies were conducted in seven subjects using the bolus/infusion approach designed for attaining steady state in blood and brain 2 hours after the initial [18F]altanserin administration. Three hours after commencement of radiotracer administration, 0.25 mg/kg of the selective serotonin reuptake inhibitor, citalopram (Lundbeck, Valby, Denmark), was administered to all subjects as a constant infusion for 20 minutes. To reduce 5-HT1A–mediated autoinhibition of cortical 5-HT release, four of the seven subjects were pretreated with the partial 5-HT1A agonist pindolol for 3 days at an increasing oral dose (25 mg on the day of scanning). In each subject, the baseline condition (120 to 180 minutes) was compared with the stimulated condition (195 to 300 minutes). Despite a pronounced increase in plasma prolactin and two subjects reporting hot flushes compatible with an 5-HT–induced adverse effect, cortical [18F]altanserin binding was insensitive to the citalopram challenge, even after pindolol pretreatment. The biochemical and cellular events possibly affecting the unsuccessful translation of the citalopram/pindolol challenge into a change in 5-HT2A receptor binding of [18F]altanserin are discussed.

scholarly journals Quantification of PET infusion studies without true equilibrium: A tissue clearance correction

2019 ◽  
Vol 40 (4) ◽  
pp. 860-874
Author(s):  
Ansel T Hillmer ◽  
Richard E Carson
Keyword(s):  
Positron Emission Tomography ◽  
Data Analysis ◽  
Brain Regions ◽  
Distribution Volume ◽  
Emission Tomography ◽  
Constant Infusion ◽  
Scanning Time ◽  
Positron Emission ◽  
Study Population ◽  
True Equilibrium

In some positron emission tomography (PET) studies, a reversibly binding radioligand is administered as a constant infusion to establish true equilibrium for quantification. This approach reduces scanning time and simplifies data analysis, but assumes similar behavior of the radioligand in plasma across the study population to establish true equilibrium in all subjects. Bias in outcome measurements can result if this assumption is not met. This work developed and validated a correction that reduces bias in total distribution volume ( VT) estimates when true equilibrium is not present. This correction, termed tissue clearance correction (TCC), took the form [Formula: see text], where β is the radioligand clearance rate in tissue, γ is a radiotracer-specific constant, and VT(A) is the apparent VT. Simulations characterized the robustness of TCC across imperfect values of γ and β and demonstrated reduction to false positive rates. This approach was validated with human infusion data for three radiotracers: [18F]FPEB, (−)-[18F]flubatine, and [11C]UCB-J. TCC reduced bias in VT estimates for all radiotracers and significantly reduced intersubject variance in VT for [18F]FPEB data in some brain regions. Thus, TCC improves quantification of data acquired from PET infusion studies.

scholarly journals Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography. Part II: Amphetamine-Induced Dopamine Release in the Functional Subdivisions of the Striatum

2003 ◽  
Vol 23 (3) ◽  
pp. 285-300 ◽  
Author(s):  
Diana Martinez ◽  
Mark Slifstein ◽  
Allegra Broft ◽  
Osama Mawlawi ◽  
Dah-Ren Hwang ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Regional Differences ◽  
Dopamine Release ◽  
Region Of Interest ◽  
Volume Effect ◽  
Emission Tomography ◽  
Constant Infusion ◽  
Positron Emission ◽  
Amphetamine Administration ◽  
Striatal Function

The human striatum is functionally organized into limbic, associative, and sensorimotor subdivisions, which process information related to emotional, cognitive, and motor function. Dopamine projections ascending from the midbrain provide important modulatory input to these striatal subregions. The aim of this study was to compare activation of dopamine D2 receptors after amphetamine administration in the functional subdivisions of the human striatum. D2 receptor availability (V3″) was measured with positron emission tomography and [11C]raclopride in 14 healthy volunteers under control conditions and after the intravenous administration of amphetamine (0.3 mg/kg). For each condition, [11C]raclopride was administered as a priming bolus followed by constant infusion, and measurements of D2 receptor availability were obtained under sustained binding equilibrium conditions. Amphetamine induced a significantly larger reduction in D2 receptor availability (ΔV3″) in limbic (ventral striatum, −15.3 ± 11.8%) and sensorimotor (postcommissural putamen, −16.1 ± 9.6%) regions compared with associative regions (caudate and precommissural putamen, −8.1 ± 7.2%). Results of this region-of-interest analysis were confirmed by a voxel-based analysis. Correction for the partial volume effect showed even greater differences in ΔV3″ between limbic (−17.8 ± 13.8%), sensorimotor (−16.6 ± 9.9%), and associative regions (−7.5 ± 7.5%). The increase in euphoria reported by subjects after amphetamine was associated with larger ΔV3″ in the limbic and sensorimotor regions, but not in the associative regions. These results show significant differences in the dopamine response to amphetamine between the functional subdivisions of the human striatum. The mechanisms potentially accounting for these regional differences in amphetamine-induced dopamine release within the striatum remain to be elucidated, but may be related to the asymmetrical feed-forward influences mediating the integration of limbic, cognitive, and sensorimotor striatal function via dopamine cell territories in the ventral midbrain.

scholarly journals Monash DaCRA fPET-fMRI: A DAtaset for Comparison of Radiotracer Administration for high temporal resolution functional FDG-PET

2021 ◽  
Author(s):  
Sharna D Jamadar ◽  
Emma X Liang ◽  
Shenjun Zhong ◽  
Phillip GD Ward ◽  
Alexandra Carey ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Glucose Uptake ◽  
Temporal Resolution ◽  
Emission Tomography ◽  
Constant Infusion ◽  
High Temporal Resolution ◽  
Bolus Infusion ◽  
Bold Fmri ◽  
Infusion Group ◽  
Positron Emission

Background: Functional [18F]-fluorodeoxyglucose positron emission tomography (FDG-fPET) is a new approach for measuring glucose uptake in the human brain. The goal of FDG-fPET is to maintain a constant plasma supply of radioactive FDG in order to track, with high temporal resolution, the dynamic uptake of glucose during neuronal activity that occurs in response to a task or at rest. FDG-fPET has most often been applied in simultaneous BOLD-fMRI/FDG-fPET (blood oxygenation level dependent functional MRI fluorodeoxyglucose functional positron emission tomography) imaging. BOLD-fMRI/FDG-fPET provides the capability to image the two primary sources of energetic dynamics in the brain, the cerebrovascular haemodynamic response and cerebral glucose uptake. Findings: In this Data Note, we describe an open access dataset, Monash DaCRA fPET-fMRI, which contrasts three radiotracer administration protocols for FDG-fPET: bolus, constant infusion, and hybrid bolus/infusion. Participants (n=5 in each group) were randomly assigned to each radiotracer administration protocol and underwent simultaneous BOLD-fMRI/FDG-fPET scanning while viewing a flickering checkerboard. The Bolus group received the full FDG dose in a standard bolus administration; the Infusion group received the full FDG dose as a slow infusion over the duration of the scan, and the Bolus-Infusion group received 50% of the FDG dose as bolus and 50% as constant infusion. We validate the dataset by contrasting plasma radioactivity, grey matter mean uptake, and task-related activity in the visual cortex. Conclusions: The Monash DaCRA fPET-fMRI dataset provides significant re-use value for researchers interested in the comparison of signal dynamics in fPET, and its relationship with fMRI task-evoked activity.

scholarly journals Constant Infusion Radiotracer Administration for High Temporal Resolution Positron Emission Tomography (PET) of the Human Brain: Application to [18F]-Fluorodexoyglucose PET (FDG-PET)

2019 ◽  
Author(s):  
Sharna D Jamadar ◽  
Phillip GD Ward ◽  
Alexandra Carey ◽  
Richard McIntyre ◽  
Linden Parkes ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Temporal Resolution ◽  
Fdg Pet ◽  
Blood Oxygenation ◽  
Emission Tomography ◽  
Constant Infusion ◽  
High Temporal Resolution ◽  
Bolus Administration ◽  
Positron Emission

AbstractFunctional Positron Emission Tomography (fPET) provides a method to track molecular dynamics in the human brain. With a radioactively labelled glucose-analogue, [18F]-flurodeoxyglucose (FDG-fPET), it is now possible to index the dynamics of glucose metabolism with temporal resolutions approaching those of functional magnetic resonance imaging (fMRI). This direct measure of glucose uptake has enormous potential for understanding normal and abnormal brain function, and probing the effects of metabolic and neurodegenerative diseases. Further, new advances in hybrid MR-PET hardware makes it possible to capture fluctuations in glucose and blood oxygenation simultaneously using fMRI and FDG-fPET.The temporal resolution and signal-to-noise of the FDG-fPET images is critically dependent upon the administration of the radioactive tracer. In this work we present two alternative continuous infusion protocols and compare them to a traditional bolus approach. We detail a method for acquiring blood samples, time-locking PET, MRI and experimental stimulus, and administrating the non-traditional tracer delivery. By applying a visual stimulus, we demonstrate cortical maps of the glucose-response to external stimuli on an individual level with a temporal resolution of 16-seconds.SummaryRadiotracer infusion protocols for positron emission tomography (PET) provide improved temporal resolution over bolus administration. Here, we describe radiotracer administration for two protocols, constant infusion and bolus plus infusion protocol. We compare this to the standard bolus administration protocol. Using [18-F] fluorodeoxyglucose PET (FDG-PET) as an example, we show that temporal resolutions of approximately 16sec are achievable using these protocols.

scholarly journals Kinetic Modeling of N-[11C]Methylpiperidin-4-yl Propionate: Alternatives for Analysis of an Irreversible Positron Emission Tomography Tracer for Measurement of Acetylcholinesterase Activity in Human Brain

1999 ◽  
Vol 19 (10) ◽  
pp. 1150-1163 ◽  
Author(s):  
Robert A. Koeppe ◽  
Kirk A. Frey ◽  
Scott E. Snyder ◽  
Phillipp Meyer ◽  
Michael R. Kilbourn ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Ache Activity ◽  
Visual Stimulation ◽  
Emission Tomography ◽  
Hydrolysis Rate ◽  
Constant Infusion ◽  
Order Kinetic ◽  
Time Activity ◽  
Positron Emission ◽  
Least Squares Fit

N-[11C]Methylpiperidin-4-yl propionate ([11C]PMP) is a substrate for hydrolysis by acetylcholinesterase (AChE). This work evaluates kinetic analysis alternatives for estimation of relative AChE activity using dynamic positron emission tomography (PET) studies of [11C]PMP. The PET studies were performed on three groups of subjects: (1) 12 normal volunteer subjects, aged 20 to 45 years, who received a single intravenous injection of 16 to 32 mCi of [11C]PMP; (2) six subjects, aged 21 to 44 years, who received two 16-mCi injections of [11C]PMP (baseline and visual stimulation, respectively); and (3) five subjects, aged 24 to 40 years, who received two 16-mCi injections separated by 200 minutes (baseline and after a 1-hour constant infusion of 1.5 mg of physostigmine, respectively). Dynamic acquisition consisted of a 17-frame sequence over 80 minutes. All analysis methods were based on a first-order kinetic model consisting of two tissue compartments with the parameter k3‘ representing PMP hydrolysis, being the index of AChE activity. Four different schemes were used to estimate k3: (1) an unconstrained nonlinear least-squares fit estimating blood—brain barrier transport parameters, K1 and k2, in addition to the hydrolysis rate constant k3; (2) and (3), two methods of constraining the fit by fixing the volume of distribution of free tracer (DVfree); and (4), a direct estimation of k3 without use of an arterial input function based on the shape of the tissue time—activity curve alone. Results showed that k3 values from the unconstrained fitting and no input methods were estimated with similar accuracy, whereas the two methods using DVfree constraints yielded similar results. The authors conclude that the optimal analysis method for [11C]PMP differs as a function of AChE activity. All four methods gave precise measures of k3 in regions with low AChE activity (~10% coefficient of variation in cortex), but surprisingly, with unconstrained methods yielding estimates with lower variability than constrained methods. In regions with moderate to high AChE activity, constrained methods were required to yield meaningful estimates and were superior to the unconstrained methods.

Deciphering PDT-induced inflammatory responses using real-time FDG-PET in a mouse tumour model

2014 ◽  
Vol 13 (10) ◽  
pp. 1434-1443
Author(s):  
Nicole Cauchon ◽  
Haroutioun M. Hasséssian ◽  
Eric Turcotte ◽  
Roger Lecomte ◽  
Johan E. van Lier
Keyword(s):  
Positron Emission Tomography ◽  
Real Time ◽  
Fdg Pet ◽  
Inflammatory Responses ◽  
Metabolic Changes ◽  
Emission Tomography ◽  
Constant Infusion ◽  
Positron Emission ◽  
Mouse Tumour

Dynamic positron emission tomography (PET), combined with constant infusion of 2-deoxy-2-[18F]fluoro-d-glucose (FDG), enables real-time monitoring of transient metabolic changesin vivo, which can serve to understand the underlying physiology.

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