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.

scholarly journals Noninvasive and Quantitative Monitoring of the Distributions and Kinetics of MicroRNA-Targeting Molecules in Vivo by Positron Emission Tomography

2019 ◽  
Vol 16 (4) ◽  
pp. 1507-1515 ◽  
Author(s):  
Jussi Mäkilä ◽  
Anu Kiviniemi ◽  
Tiina Saanijoki ◽  
Heidi Liljenbäck ◽  
Meeri Käkelä ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Positron Emission ◽  
Quantitative Monitoring ◽  
Kinetics Of

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 Kinetic Modeling of [11C]Raclopride: Combined PET-Microdialysis Studies

1997 ◽  
Vol 17 (9) ◽  
pp. 932-942 ◽  
Author(s):  
Christopher J. Endres ◽  
Bhaskar S. Kolachana ◽  
Richard C. Saunders ◽  
Tom Su ◽  
Daniel Weinberger ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Specific Binding ◽  
Compartment Model ◽  
Emission Tomography ◽  
Extended Model ◽  
Simulation Studies ◽  
Time Activity ◽  
Endogenous Dopamine ◽  
Positron Emission

The in vivo binding of D2 receptor ligands can be affected by agents that alter the concentration of endogenous dopamine. To define a more explicit relation between dopamine and D2 receptor binding, the conventional compartment model for reversible ligands has been extended to account for a time-varying dopamine pulse. This model was tested with [11C]raclopride positron emission tomography and dopamine microdialysis data that were acquired simultaneously in rhesus monkeys. The microdialysis data were incorporated into the model assuming a proportional relation to synaptic dopamine. Positron emission tomography studies used a bolus-plus-infusion tracer delivery with amphetamine given at 40 minutes to induce dopamine release. The extended model described the entire striatal time–activity curve, including the decrease in radioactivity concentration after an amphetamine-induced dopamine pulse. Based on these results, simulation studies were performed using the extended model. The simulation studies showed that the percent decrease in specific binding after amphetamine measured with the bolus-plus-infusion protocol correlates well with the integral of the postamphetamine dopamine pulse. This suggests that changes in specific binding observed in studies in humans can be interpreted as being linearly proportional to the integral of the amphetamine-induced dopamine pulse.

scholarly journals A new noninvasive quantification of renal blood flow with N-13 ammonia, dynamic positron emission tomography, and a two-compartment model.

1992 ◽  
Vol 3 (6) ◽  
pp. 1295-1306
Author(s):  
B C Chen ◽  
G Germano ◽  
S C Huang ◽  
R A Hawkins ◽  
H W Hansen ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Pet Imaging ◽  
Renal Cortex ◽  
Compartment Model ◽  
Regions Of Interest ◽  
Emission Tomography ◽  
Dynamic Positron Emission Tomography ◽  
Positron Emission ◽  
Two Compartment Model

In order to determine if dynamic positron emission tomography (PET) and N-13 ammonia can be used to quantitate regional RBF (rRBF) noninvasively, six anesthetized dogs were examined with PET imaging after an iv bolus administration of 5 mCi of N-13 ammonia. Renal time activity curves and the arterial input function were derived from regions of interest drawn over the renal cortex and abdominal aorta, respectively. For calculation of rRBF, less than 120 s of the initial data were used to minimize contamination by plasma metabolites of N-13 radioactivity. rRBF was quantitated with a two-compartment model, and the results were compared with simultaneously acquired microsphere blood flow measurement. Fourteen experiments were performed in six dogs, and four regions of interest on renal cortex were selected on each PET image. RBF derived from dynamic PET imaging with N-13 ammonia was linearly related to microsphere (MS) values (rRBF = 1.06 x MS - 0.17; r = 0.91). Mean rRBF in the canine experiments was 4.0 mL/min/g. The results indicate that dynamic N-13 ammonia renal PET can provide noninvasively quantitative rRBF.

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