Neuroreceptor Assay with Positron Emission Tomography: Equilibrium versus Dynamic Approaches

Huang, Sung‐Cheng; Barrio, Jorge R.; Phelps, Michael E.

doi:10.1038/jcbfm.1986.96

Cited by 150 publications

(62 citation statements)

References 21 publications

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“…However, the model structure may differ depending on the organ, the molecule, or the exper imental protocol used. For example, the binding of ligands can be reversible or not, a nonspecifically bound ligand compartment may be introduced [see detailed and critical reviews of the quantitative models in Huang et al (1986), Perlmutter et al (1986), and Logan et al (1987), for example]. Ac cording to the model structure, the number of model parameters used in this field are four to eight, which usually must be identified from a single curve.…”

Section: Discussionmentioning

confidence: 99%

Kinetic Analysis of Central [⁷⁶Br]Bromolisuride Binding to Dopamine D₂ Receptors Studied by PET

Delforge

Loc’h

Hantraye

et al. 1991

J Cereb Blood Flow Metab

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Summary:The in vivo kinetic analysis of dopamine D 2 receptors was obtained in baboon brain using positron emission tomography (PET) and C6Brjbromolisuride W6BrjBLlS) as radioligand. An injection of a trace amount of C6BrjBLlS was followed 3 h later by an injec tion of a mixture of C6BrjBLlS and BLIS in the same syringe (coinjection experiment). A third injection per formed at 6 h was either an excess of unlabeled ligand (displacement experiment) or a second coinjection. This protocol allowed us to evaluate in the striatum of each animal and after a single experiment the quantity of avail able receptors (B:naJ and the kinetic parameters includ ing the association and dissociation rate constants (k + I V R and k _ l' respectively, where V R is the volume of reac tion). The cerebellum data were fitted using a model with out specific binding. All the parameters were estimatedThe dopaminergic system was the first neuro transmission system in which it was possible to im age receptors, stored neurotransmitters, and neuro transmitter reuptake mechanisms. For a long time, most researchers endorsed the hypothesis that there were at least two major dopamine receptor types: DJ receptors linked to the stimulation of ade nylate cyclase and D2 receptors linked to the inhi bition of this enzyme (Kebabian and CaIne, 1979 Abbreviations used: BLIS, bromolisuride ; PET, po sitron emission tomography; ROI, region of interest; TLC, thin layer chromatography. 914using nonlinear mathematical models of the ligand receptor interactions including or not including nonspe cific binding. The plasma time-concentration curve was used as an input function after correction for the metab olites. An estimate of standard errors was obtained for each PET study and for each identified parameter using the covariance matrix. The average values of B:n ax and Kd V R were 73 ± II pmollml tissue and 1.9 ± 0.9 pmollml, respectively. The nonspecific binding was identifiable in the experiment where the last injection corresponded to a second coinjection. We found that �6% of the striatal binding was nonspecific after a tracer injection of C6Brj BLIS. The nonspecific binding appeared to be reversible in the striatum but irreversible in the cerebellum.

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Section: Discussionmentioning

confidence: 99%

Kinetic Analysis of Central [⁷⁶Br]Bromolisuride Binding to Dopamine D₂ Receptors Studied by PET

Delforge

Loc’h

Hantraye

et al. 1991

J Cereb Blood Flow Metab

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“…The part of this model corresponding to befloxatone kinetics is derived from the usual nonequilibrium nonlinear model (Mintun et al, 1984;Huang et al, 1986). It includes four compartments (unmetabolized ligand in plasma, free ligand in the tissue, ligand specifically bound to receptor sites, and nonspecific binding; Figure 1) and seven parameters (the MAO binding site concentration (B 0 max ) and six kinetic parameters describing the kinetics between the compartments (K 1 , k 2 , k 5 , k 6 and the apparent association and dissociation rate constants k on /V R , and k off )).…”

Section: The Ligand-receptor Modelmentioning

confidence: 99%

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [¹¹C]befloxatone and the Multi-Injection Approach

Bottlaender

Valette

Delforge

et al. 2009

J Cereb Blood Flow Metab

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[ 11 C]befloxatone is a high-affinity, reversible, and selective radioligand for the in vivo visualization of the monoamine oxidase A (MAO-A) binding sites using positron emission tomography (PET). The multi-injection approach was used to study in baboons the interactions between the MAO-A binding sites and [ 11 C]befloxatone. The model included four compartments and seven parameters. The arterial plasma concentration, corrected for metabolites, was used as input function. The experimental protocol-three injections of labeled and/or unlabeled befloxatone-allowed the evaluation of all the model parameters from a single PET experiment. In particular, the brain regional concentrations of the MAO-A binding sites (B 0 max ) and the apparent in vivo befloxatone affinity (K d ) were estimated in vivo for the first time. A high binding site density was found in almost all the brain structures (170±39 and 194±26 pmol/mL in the frontal cortex and striata, respectively, n = 5). The cerebellum presented the lowest binding site density (66 ± 13 pmol/mL). Apparent affinity was found to be similar in all structures (K d V R = 6.4±1.5 nmol/L). This study is the first PET-based estimation of the B max of an enzyme.

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“…A graphical analysis method was applied for quantitation of in vivo dopamine D 2 receptor binding (Huang et al 1986). Again, the cerebellum was used as a reference region as discussed above.…”

Section: Kinetic Analysis Of In Vivo Receptor Bindingmentioning

confidence: 99%

Sustained Withdrawal Allows Normalization of In Vivo [11C]N-Methylspiperone Dopamine D2 Receptor Binding after Chronic Binge Cocaine A Positron Emission Tomography Study in Rats

Maggos

Tsukada

Kakiuchi

et al. 1998

Neuropsychopharmacology

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Neuroreceptor Assay with Positron Emission Tomography: Equilibrium versus Dynamic Approaches

Cited by 150 publications

References 21 publications

Kinetic Analysis of Central [⁷⁶Br]Bromolisuride Binding to Dopamine D₂ Receptors Studied by PET

Kinetic Analysis of Central [⁷⁶Br]Bromolisuride Binding to Dopamine D₂ Receptors Studied by PET

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [¹¹C]befloxatone and the Multi-Injection Approach

Sustained Withdrawal Allows Normalization of In Vivo [11C]N-Methylspiperone Dopamine D2 Receptor Binding after Chronic Binge Cocaine A Positron Emission Tomography Study in Rats

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Neuroreceptor Assay with Positron Emission Tomography: Equilibrium versus Dynamic Approaches

Cited by 150 publications

References 21 publications

Kinetic Analysis of Central [76Br]Bromolisuride Binding to Dopamine D2 Receptors Studied by PET

Kinetic Analysis of Central [76Br]Bromolisuride Binding to Dopamine D2 Receptors Studied by PET

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [11C]befloxatone and the Multi-Injection Approach

Sustained Withdrawal Allows Normalization of In Vivo [11C]N-Methylspiperone Dopamine D2 Receptor Binding after Chronic Binge Cocaine A Positron Emission Tomography Study in Rats

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Kinetic Analysis of Central [⁷⁶Br]Bromolisuride Binding to Dopamine D₂ Receptors Studied by PET

Kinetic Analysis of Central [⁷⁶Br]Bromolisuride Binding to Dopamine D₂ Receptors Studied by PET

In vivoQuantification of Monoamine Oxidase A in Baboon Brain: A PET Study Using [¹¹C]befloxatone and the Multi-Injection Approach