Interaction of a Muscarinic Cholinergic Agonist on Acetylcholine and Dopamine Receptors in the Monkey Brain Studied with Positron Emission Tomography

2002 ◽  
Vol 13 (4) ◽  
pp. 199-204 ◽  
Author(s):  
Per Hartvig ◽  
Agneta Nordberg ◽  
Richard Torstenson ◽  
Pernilla Sjöberg ◽  
Karl Johan Fasth ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Dopamine Receptors ◽  
Emission Tomography ◽  
Monkey Brain ◽  
Cholinergic Agonist ◽  
Positron Emission ◽  
Muscarinic Cholinergic

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.

Sight and Insight: Regional Cerebral Metabolic Activity in Schizophrenia Visualised by Positron Emission Tomography, and Competing Neurodevelopmental Perspectives

1990 ◽  
Vol 156 (5) ◽  
pp. 615-619 ◽  
Author(s):  
John L. Waddington
Keyword(s):  
Positron Emission Tomography ◽  
Psychiatric Disorders ◽  
Dopamine Receptors ◽  
Metabolic Activity ◽  
New Technology ◽  
Emission Tomography ◽  
Brain Dopamine ◽  
The Past ◽  
Positron Emission ◽  
Schizophrenic Patients

Over the past several years there has emerged a family of highly sophisticated but technically complex procedures for the visualisation of a range of cerebral functions in living man (Andreasen, 1988). The images they produce are so beguiling not just because of their potential to give new insights into the pathophysiology and treatment of major psychiatric disorders, but because they convey information through a quite fundamental modality: people are only convinced by what they can see. However, initial applications of such new technology have appeared just as likely to generate new questions and contradictions as to provide answers to current issues. This is readily illustrated by recent studies on the imaging of brain dopamine receptors in schizophrenic patients by positron emission tomography (PET) (see Waddington, 1989a).

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.

Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics

Science ◽  
1986 ◽  
Vol 234 (4783) ◽  
pp. 1558-1563 ◽  
Author(s):  
D. Wong ◽  
H. Wagner ◽  
L. Tune ◽  
R. Dannals ◽  
G. Pearlson ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Dopamine Receptors ◽  
Emission Tomography ◽  
D2 Dopamine Receptors ◽  
Positron Emission ◽  
Drug Naïve
Sign in / Sign up

Export Citation Format

Share Document