scholarly journals The Quantitative Analysis of D2-Dopamine Receptors in Baboon Striatum in vivo with 3-N-[2'-18F]Fluoroethylspiperone Using Positron Emission Tomography

1990 ◽  
Vol 10 (5) ◽  
pp. 720-726 ◽  
Author(s):  
S. Jovkar ◽  
K. Wienhard ◽  
G. Pawlik ◽  
H. H. Coenen
Keyword(s):  
Positron Emission Tomography ◽  
Kinetic Model ◽  
Dopamine Receptors ◽  
Specific Activity ◽  
Emission Tomography ◽  
Parameter Estimates ◽  
Model Parameters ◽  
Positron Emission ◽  
Model Configuration

We used the ligand 3- N-[2'-18F]fluoroethylspiperone (FESP), which binds to D2-dopamine receptors in the striatum, and positron emission tomography (PET) to quantify striatal D2-dopamine densities ( Bmax) and binding kinetics in baboon brain in vivo. Sequential PET scans were obtained for 4 h post injection. Various similar models based on a nonlinear kinetic four-compartment model that takes into account the effect of ligand specific activity were used. We investigated the effect of exact model configuration on the reliability of Bmax and other kinetic transfer coefficients. We found that with the ligand FESP and dynamic PET studies, the estimated values of Bmax and other model parameters are sensitive to the choice of model configuration, ligand specific activity, and data analysis technique. The limitations of the reliability of parameter estimates in a complex kinetic model for receptor ligands were studied in simulation calculations. Results showed that the accuracy of estimated values of Bmax is affected by both the ligand binding properties and the injected dose of ligand. The estimated average value of kinetic model parameters was as follows: ligand-receptor dissociation constant k4 = 0.0080 min−1; the product of ligand-receptor association constant and fraction of ligand available to bind to specific receptors f2 ka = 0.0052 (min n M)−1; and D2-dopamine receptor density Bmax = 37.5 pmol g−1.

scholarly journals Dual-[11C]Tracer Single-Acquisition Positron Emission Tomography Studies

2001 ◽  
Vol 21 (12) ◽  
pp. 1480-1492 ◽  
Author(s):  
Robert A. Koeppe ◽  
David M. Raffel ◽  
Scott E. Snyder ◽  
Edward P. Ficaro ◽  
Michael R. Kilbourn ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Computer Simulations ◽  
Emission Tomography ◽  
Parameter Estimates ◽  
Model Parameters ◽  
Tracer Injection ◽  
Positron Emission ◽  
Dynamic Scan ◽  
Dual Tracer

The ability to study multiple physiologic processes of the brain simultaneously within the same subject would provide a new means to explore the interactions between neurotransmitter systems in vivo. Currently, examination of two distinct neuropharmacologic measures with positron emission tomography (PET) necessitates performing two separate scans spaced in time to allow for radionuclide decay. The authors present results from a dual-tracer PET study protocol using a single dynamic-scan acquisition where the injections of two tracers are offset by several minutes. Kinetic analysis is used to estimate neuropharmacologic parameters for both tracers simultaneously using a combined compartmental model configuration. This approach results in a large reduction in total study time of nearly 2 hours for carbon-11–labeled tracers. As multiple neuropharmacologic measures are obtained at nearly the same time, interventional protocols involving a pair of dual-tracer scans become feasible in a single PET session. Both computer simulations and actual human PET studies were performed using combinations of three different tracers: [11C]flumazenil, N-[11C]methylpiperidinyl propionate, and [11C]dihydrotetrabenazine. Computer simulations of tracer-injection separations of 10 to 30 minutes showed the feasibility of the approach for separations down to 15 to 20 minutes or less. Dual-tracer PET studies were performed in 32 healthy volunteers using injection separations of 10, 15, or 20 minutes. Model parameter estimates for each tracer were similar to those obtained from previously performed single-injection studies. Voxel-by-voxel parametric images were of good quality for injections spaced by 20 minutes and were nearly as good for 15-minute separations, but were degraded noticeably for some model parameters when injections were spaced by only 10 minutes. The authors conclude that dual-tracer single-scan PET is feasible, yields accurate estimates of multiple neuropharmacologic measures, and can be implemented with a number of different radiotracer pairs.

scholarly journals Muscarinic Cholinergic Receptor Measurements with [18F]FP-TZTP: Control and Competition Studies

1998 ◽  
Vol 18 (10) ◽  
pp. 1130-1142 ◽  
Author(s):  
Richard E. Carson ◽  
Dale O. Kiesewetter ◽  
Elaine Jagoda ◽  
Margaret G. Der ◽  
Peter Herscovitch ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Basal Ganglia ◽  
Specific Binding ◽  
Emission Tomography ◽  
Ache Inhibitor ◽  
Parameter Estimates ◽  
Tracer Injection ◽  
Positron Emission ◽  
Muscarinic Cholinergic

[18F]Fluoropropyl-TZTP (FP-TZTP) is a subtype-selective muscarinic cholinergic ligand with potential suitability for studying Alzheimer's disease. Positron emission tomography studies in isofluorane-anesthetized rhesus monkeys were performed to assess the in vivo behavior of this radiotracer. First, control studies (n = 11) were performed to characterize the tracer kinetics and to choose an appropriate model using a metabolite-corrected arterial input function. Second, preblocking studies (n = 4) with unlabeled FP-TZTP were used to measure nonspecific binding. Third, the sensitivity of [18F]FP-TZTP binding to changes in brain acetylcholine (ACh) was assessed by administering physostigmine, an acetylcholinesterase (AChE) inhibitor, by intravenous infusion (100 to 200 μg·kg−1·h−1) beginning 30 minutes before tracer injection (n = 7). Tracer uptake in the brain was rapid with K1 values of 0.4 to 0.6 mL·min−1·mL−1 in gray matter. A model with one tissue compartment was chosen because reliable parameter estimates could not be obtained with a more complex model. Volume of distribution ( V) values, determined from functional images created by pixel-by-pixel fitting, were very similar in cortical regions, basal ganglia, and thalamus, but significantly lower ( P < 0.01) in the cerebellum, consistent with the distribution of M2 cholinergic receptors. Preblocking studies with unlabeled FP-TZTP reduced V by 60% to 70% in cortical and subcortical regions. Physostigmine produced a 35% reduction in cortical specific binding ( P < 0.05), consistent with increased ACh competition. The reduction in basal ganglia (12%) was significantly smaller ( P < 0.05), consistent with its markedly higher AChE activity. These studies indicate that [18F]FP-TZTP should be useful for the in vivo measurement of muscarinic receptors with positron emission tomography.

scholarly journals Positron Emission Tomography Compartmental Models: A Basis Pursuit Strategy for Kinetic Modeling

2002 ◽  
Vol 22 (12) ◽  
pp. 1425-1439 ◽  
Author(s):  
Roger N. Gunn ◽  
Steve R. Gunn ◽  
Federico E. Turkheimer ◽  
John A. D. Aston ◽  
Vincent J. Cunningham
Keyword(s):  
Positron Emission Tomography ◽  
Kinetic Modeling ◽  
Impulse Response Function ◽  
Emission Tomography ◽  
Basis Pursuit ◽  
Parameter Estimates ◽  
Binding Studies ◽  
General Applicability ◽  
Positron Emission

A kinetic modeling approach for the quantification of in vivo tracer studies with dynamic positron emission tomography (PET) is presented. The approach is based on a general compartmental description of the tracer's fate in vivo and determines a parsimonious model consistent with the measured data. The technique involves the determination of a sparse selection of kinetic basis functions from an overcomplete dictionary using the method of basis pursuit denoising. This enables the characterization of the systems impulse response function from which values of the systems macro parameters can be estimated. These parameter estimates can be obtained from a region of interest analysis or as parametric images from a voxel-based analysis. In addition, model order estimates are returned that correspond to the number of compartments in the estimated compartmental model. Validation studies evaluate the methods performance against two preexisting data led techniques, namely, graphical analysis and spectral analysis. Application of this technique to measured PET data is demonstrated using [11C]diprenorphine (opiate receptor) and [11C]WAY-100635 (5-HT1A receptor). Although the method is presented in the context of PET neuroreceptor binding studies, it has general applicability to the quantification of PET/SPECT radiotracer studies in neurology, oncology, and cardiology.

In Vivo Measurement of Dopamine Receptors in Human Brain by Positron Emission Tomography Age and Sex Differences

1988 ◽  
Vol 515 (1 Central Deter) ◽  
pp. 203-214 ◽  
Author(s):  
DEAN F. WONG ◽  
EMMANUEL P. BROUSSOLLE ◽  
GARY WAND ◽  
VICTOR VILLEMAGNE ◽  
ROBERT F. DANNALS ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Sex Differences ◽  
Human Brain ◽  
Dopamine Receptors ◽  
Emission Tomography ◽  
In Vivo Measurement ◽  
Positron Emission ◽  
Age And Sex

scholarly journals Erratum

1992 ◽  
Vol 12 (5) ◽  
pp. 885-885 ◽  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Specific Activity ◽  
Opiate Receptor ◽  
Emission Tomography ◽  
Parameter Estimates ◽  
Positron Emission ◽  
Receptor Concentration ◽  
Tracer Kinetic

Quantification of Human Opiate Receptor Concentration and Affinity Using High and Low Specific Activity [11C]Diprenorphine and Positron Emission Tomography Bernard Sadzot, Julie C. Price, Helen S. Mayberg, Kenneth H. Douglass, Robert F. Dannals, John R. Lever, Hayden T. Ravert, Alan A. Wilson, Henry N. Wagner, Jr., Marc A. Feldman, and J. James Frost [originally published in Journal of Cerebral Blood Flow and Metabolism 1991;11(2):204–219] Due to errors in the PET calibration factors, the published values of some of the parameter estimates are inaccurate. The correct values of Bmax and KD are 1.4 times and 0.4 times the published value, respectively. The correct values of Kl and Ktfk2 are 3.2 times the published value. Accordingly, the values of konf2 and f2 are 0.7 and 0.3 times the published value, respectively. The values of k2′ k3′ and k4 are correct. These quantitative errors in the parameter estimates do not affect the overall strategy for the application of tracer kinetic modeling nor the identification of the optimal fitting strategy. The authors regret these errors.

scholarly journals Models for in vivo Kinetic Interactions of Dopamine D2-Neuroreceptors and 3-(2'-[18F]Fluoroethyl)Spiperone Examined with Positron Emission Tomography

1989 ◽  
Vol 9 (6) ◽  
pp. 840-849 ◽  
Author(s):  
Mark M. Bahn ◽  
Sung-Cheng Huang ◽  
Randall A. Hawkins ◽  
Nagichettiar Satyamurthy ◽  
John M. Hoffman ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Nonlinear Model ◽  
Compartment Model ◽  
Emission Tomography ◽  
Positron Emission ◽  
Two Compartment Model ◽  
Model Configuration ◽  
Net Uptake ◽  
Kinetics Of

The in vivo tracer kinetics of 3-(2apos;-[18F]fluoroethyl)spiperone (FESP) in the caudate/striatum and cerebellar regions of the human and monkey brain were studied with positron emission tomography (PET). The minimal model configuration that can describe the kinetics was determined statistically. Three two-compartment model configurations were found to be suitable for describing the kinetics in caudate/striatum and cerebellum: (1) a nonlinear model (five parameters) applicable to studies using nontracer (partially saturating) quantities of FESP in monkey striatum, (2) a linear four-parameter model applicable to the caudate/striatal and cerebellar kinetics in human and monkey studies with tracer quantities of FESP, and (3) a linear three-parameter model derived from the four-parameter model by assuming irreversible binding applicable to tracer studies of the human caudate. In the human studies, when the caudate kinetics ( n = 4) were fit by model 2 (with four parameters), the value of the in vivo ligand dissociation constant kd was found to be 0.0015 ± 0.0032/min. The three-parameter model (model 3) was found to fit the data equally well; this model is equivalent to model 2 with kd set to zero. In the monkey studies, it was found that for short (90 min) studies using tracer quantities of FESP, model 2 fit the striatal kinetics better than model 3. The parameters estimated using model 2 (four parameters) were in better agreement with those estimated by the nonlinear model (model 1) than those estimated using model 3 (three parameters). The use of a graphical approach gives estimates of the plasma–tissue fractional transport rate constant K1 and the net uptake constant K3 comparable to estimates using model 3 for both human and monkey studies.

In vivo quantitative imaging of dopamine receptors in human brain using positron emission tomography and [76Br]bromospiperone

1985 ◽  
Vol 114 (3) ◽  
pp. 267-272 ◽  
Author(s):  
Bernard Mazière ◽  
Christian Loc'h ◽  
Jean-Claude Baron ◽  
Panos Sgouropoulos ◽  
Nathalie Duquesnoy ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Dopamine Receptors ◽  
Quantitative Imaging ◽  
Emission Tomography ◽  
Positron Emission

scholarly journals Measurement of Brain pH Using 11CO2 and Positron Emission Tomography

1984 ◽  
Vol 4 (1) ◽  
pp. 8-16 ◽  
Author(s):  
R. B. Buxton ◽  
L. R. Wechsler ◽  
N. M. Alpert ◽  
R. H. Ackerman ◽  
D. R. Elmaleh ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Kinetic Model ◽  
The Body ◽  
Time Dependent ◽  
Emission Tomography ◽  
Model Parameters ◽  
Tissue Ph ◽  
Local Tissue ◽  
Positron Emission ◽  
Brain Ph

We have examined the feasibility of measuring local brain pH in vivo with 11CO2 and positron emission tomography. In particular, we have addressed two objections that have been raised against this method: the assumed need to estimate local tissue Pco2 and the rapid fixation of 11C in tissue. From a reexamination of the basic theory, we argue that after administration of 11CO2 the time-dependent distribution of 11C between tissue and blood is independent of the distribution of CO2 already in the body, making it unnecessary to estimate local tissue Pco2. Assuming that the blood–brain barrier is impermeable to bicarbonate ions, there will be equal partial pressures of 11CO2 in blood and tissue at equilibrium. To overcome the problem of fixation in the tissue we have developed a kinetic model of the time-dependent distribution of 11C that accounts for regional variations in blood flow, CO2 extraction, pH, and rate of fixation. The values of the model parameters can be estimated from sequential measurements of tissue activity concentration during administration of 11CO2. Tissue pH can then be calculated from one of the parameter values, a measurement of arterial pH, and known constants. Numerical calculations based on the kinetic model with assumed values of the parameters were used to optimize the experimental design. The calculations show that problems with fixation are much less severe with continuous infusion of activity than with bolus administration. During infusion the tissue curve depends strongly on tissue pH but only weakly on the rate of fixation. With state of the art tomographic systems it should be possible to measure tissue pH with an error of about 0.04 pH units.

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