scholarly journals Quantitation of Translocator Protein Binding in Human Brain with the Novel Radioligand [18F]-FEPPA and Positron Emission Tomography

2011 ◽  
Vol 31 (8) ◽  
pp. 1807-1816 ◽  
Author(s):  
Pablo M Rusjan ◽  
Alan A Wilson ◽  
Peter M Bloomfield ◽  
Irina Vitcu ◽  
Jeffrey H Meyer ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Specific Binding ◽  
Compartment Model ◽  
Distribution Volume ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Specific Distribution ◽  
Positron Emission

This article describes the kinetic modeling of [18F]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume ( VT), specific distribution volume ( VS), and binding potential ( BPND) demonstrated very good identifiability (based on coefficient of variation ( COV)) for all the regions of interest (ROIs) in the gray matter ( COV VT < 7%, COV VS < 8%, COV BPND < 11%). Reduction of the length of the scan to 2 hours is feasible as VS and VT showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of VT and VS was still very good with COV<10%, across high-uptake ROIs. The excellent identifiability of VT values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of VT as an appropriate and feasible outcome measure for [18F]-FEPPA.

scholarly journals Modeling [18F]MPPF Positron Emission Tomography Kinetics for the Determination of 5-Hydroxytryptamine(1A) Receptor Concentration with Multiinjection

2002 ◽  
Vol 22 (6) ◽  
pp. 753-765 ◽  
Author(s):  
Nicolas Costes ◽  
Isabelle Merlet ◽  
Luc Zimmer ◽  
Franck Lavenne ◽  
Luc Cinotti ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Arterial Input Function ◽  
Compartment Model ◽  
Dissociation Rate ◽  
Distribution Volume ◽  
Emission Tomography ◽  
Binding Potential ◽  
Imaging Data ◽  
Positron Emission ◽  
Receptor Concentration

The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2' -methoxyphenyl)-1-[2' -(N-2“-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5-hydroxytryptamine(1A) (5-HT1A) receptors has been established in animals and humans. The authors quantified the parameters of ligand-receptor exchanges using a double-injection protocol. After injection of a tracer and a coinjection dose of [18F]MPPF, dynamic positron emission tomography (PET) data were acquired during a 160-minute session in five healthy males. These PET and magnetic resonance imaging data were coregistered for anatomical identification. A three-compartment model was used to determine six parameters: Fv (vascular fraction), K1, k2 (plasma/free compartment exchange rate), koff, kon/Vr (association and dissociation rate), Bmax (receptor concentration), and to deduce Kd (apparent equilibrium dissociation rate). The model was fitted with regional PET kinetics and arterial input function corrected for metabolites. Analytical distribution volume and binding potential were compared with indices generated by Logan-Patlak graphical analysis. The 5HT1A specificity for MPPF was evidenced. A Bmax of 2.9 pmol/mL and a Kd of 2.8 nmol/L were found in hippocampal regions, Kd and distribution volume in the free compartment were regionally stable, and the Logan binding potential was linearly correlated to Bmax. This study confirms the value of MPPF in the investigation of normal and pathologic systems involving the limbic network and 5-HT1A receptors. Standard values can be used for the simulation of simplified protocols.

scholarly journals Effects of amphetamine on the human brain opioid system – a positron emission tomography study

2013 ◽  
Vol 16 (4) ◽  
pp. 763-769 ◽  
Author(s):  
Joar Guterstam ◽  
Nitya Jayaram-Lindström ◽  
Simon Cervenka ◽  
J. James Frost ◽  
Lars Farde ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Reward System ◽  
Emission Tomography ◽  
Opioid System ◽  
Binding Potential ◽  
Positron Emission ◽  
Brain Reward ◽  
The Brain ◽  
Brain Reward System

Abstract Studies in rodents have shown that psychostimulant drugs such as cocaine and amphetamine cause endorphin release in the brain reward system. There is also evidence for the involvement of the opioid system in human psychostimulant dependence. The acute effects of an i.v. psychostimulant drug on the brain opioid system, however, have not yet been investigated in humans. We hypothesized that an i.v. dose of amphetamine as compared to placebo would cause an opioid release in the human brain reward system, measurable as a reduction of the binding potential of the µ-opioid receptor radioligand [11C]carfentanil. Ten healthy young men were examined using positron emission tomography (PET) and [11C]carfentanil in three sessions: at baseline; after placebo; after an i.v. amphetamine dose of 0.3 mg/kg bodyweight. The order of amphetamine and placebo was double-blinded and randomized. PET examinations were performed with a Siemens high resolution research tomograph. Data were analysed with the simplified reference tissue model, applying manually drawn regions of interest for every subject. Using repeated measures analysis of variance, we found no significant differences in [11C]carfentanil binding potential between amphetamine and placebo conditions in any of the investigated brain regions. In contrast to data from rodent studies and a recent study of oral amphetamine administration in humans, an i.v. dose of amphetamine does not cause any acute opioid release in healthy human subjects. The postulated role of the opioid system in mediating the effects of amphetamine needs to be further investigated in animal models of the disease as well as in patient populations.

scholarly journals Linearized Reference Tissue Parametric Imaging Methods: Application to [11C]DASB Positron Emission Tomography Studies of the Serotonin Transporter in Human Brain

2003 ◽  
Vol 23 (9) ◽  
pp. 1096-1112 ◽  
Author(s):  
Masanori Ichise ◽  
Jeih-San Liow ◽  
Jian-Qiang Lu ◽  
Akihiro Takano ◽  
Kendra Model ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Positron Emission Tomography Imaging ◽  
Emission Tomography ◽  
Binding Potential ◽  
Parametric Imaging ◽  
Reference Tissue ◽  
Parametric Images ◽  
Positron Emission ◽  
Tissue Models

The authors developed and applied two new linearized reference tissue models for parametric images of binding potential ( BP) and relative delivery ( R1) for [11C]DASB positron emission tomography imaging of serotonin transporters in human brain. The original multilinear reference tissue model (MRTMO) was modified (MRTM) and used to estimate a clearance rate ( k′2) from the cerebellum (reference). Then, the number of parameters was reduced from three (MRTM) to two (MRTM2) by fixing k′2. The resulting BP and R1 estimates were compared with the corresponding nonlinear reference tissue models, SRTM and SRTM2, and one-tissue kinetic analysis (1TKA), for simulated and actual [11C]DASB data. MRTM gave k′2 estimates with little bias (<1%) and small variability (<6%). MRTM2 was effectively identical to SRTM2 and 1TKA, reducing BP bias markedly over MRTMO from 12–70% to 1–4% at the expense of somewhat increased variability. MRTM2 substantially reduced BP variability by a factor of two or three over MRTM or SRTM. MRTM2, SRTM2, and 1TKA had R1 bias <0.3% and variability at least a factor of two lower than MRTM or SRTM. MRTM2 allowed rapid generation of parametric images with the noise reductions consistent with the simulations. Rapid parametric imaging by MRTM2 should be a useful method for human [11C]DASB positron emission tomography studies.

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 Two-Compartment Description and Kinetic Procedure for Measuring Regional Cerebral [11C]Nomifensine Uptake Using Positron Emission Tomography

1990 ◽  
Vol 10 (3) ◽  
pp. 307-316 ◽  
Author(s):  
Eric Salmon ◽  
David J. Brooks ◽  
Klaus L. Leenders ◽  
David R. Turton ◽  
Sue P. Hume ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Partition Coefficient ◽  
Cell Activity ◽  
Compartment Model ◽  
Input Function ◽  
Volume Of Distribution ◽  
Red Cells ◽  
Emission Tomography ◽  
Binding Potential ◽  
Positron Emission

S-[11C]Nomifensine ( S-[11C]NMF) is a positron-emitting tracer suitable for positron emission tomography, which binds to both dopaminergic and noradrenergic reuptake sites in the striatum and the thalamus. Modelling of the cerebral distribution of this drug has been hampered by the rapid appearance of glucuronide metabolites in the plasma, which do not cross the blood–brain barrier. To date, [11C]NMF uptake has simply been expressed as regional versus nonspecific cerebellar activity ratios. We have calculated a “free” NMF input curve from red cell activity curves, using the fact that the free drug rapidly equilibrates between red cells and plasma, while glucuronides do not enter red cells. With this free [11C]NMF input function, all regional cerebral uptake curves could be fitted to a conventional two-compartment model, defining tracer distribution in terms of [11C]NMF regional volume of distribution. Assuming that the cerebellar volume of distribution of [11C]NMF represents the nonspecific volume of distribution of the tracer in striatum and thalamus, we have calculated an equilibrium partition coefficient for [11C]NMF between freely exchanging specific and nonspecific compartments in these regions, representing its “binding potential” to dopaminergic or noradrenergic uptake sites (or complexes). This partition coefficient was lower in the striatum when the racemate rather than the active S-enantiomer of [11C]NMF was administered. In the striatum of patients suffering from Parkinson's disease and multiple-system atrophy, the specific compartmentation of S-[11C]NMF was significantly decreased compared with that of age-matched volunteers.

scholarly journals 11C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than 11C-(R)-PK11195

2017 ◽  
Vol 38 (3) ◽  
pp. 393-403 ◽  
Author(s):  
Masato Kobayashi ◽  
Teresa Jiang ◽  
Sanjay Telu ◽  
Sami S Zoghbi ◽  
Roger N Gunn ◽  
...  
Keyword(s):  
Second Generation ◽  
Specific Binding ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Arterial Blood ◽  
Plot Analysis ◽  
Positron Emission ◽  
Translocator Protein 18 Kda ◽  
Pet Scans

Positron emission tomography (PET) radioligands for translocator protein 18 kDa (TSPO) are widely used to measure neuroinflammation, but controversy exists whether second-generation radioligands are superior to the prototypical agent 11C-( R)-PK11195 in human imaging. This study sought to quantitatively measure the “signal to background” ratio (assessed as binding potential ( BPND)) of 11C-( R)-PK11195 compared to one of the most promising second-generation radioligands, 11C-DPA-713. Healthy subjects had dynamic PET scans and arterial blood measurements of radioligand after injection of either 11C-( R)-PK11195 (16 subjects) or 11C-DPA-713 (22 subjects). To measure the amount of specific binding, a subset of these subjects was scanned after administration of the TSPO blocking drug XBD173 (30–90 mg PO). 11C-DPA-713 showed a significant sensitivity to genotype in brain, whereas 11C-( R)-PK11195 did not. Lassen occupancy plot analysis revealed that the specific binding of 11C-DPA-713 was much greater than that of 11C-( R)-PK11195. The BPND in high-affinity binders was about 10-fold higher for 11C-DPA-713 (7.3) than for 11C-( R)-PK11195 (0.75). Although the high specific binding of 11C-DPA-713 suggests it is an ideal ligand to measure TSPO, we also found that its distribution volume increased over time, consistent with the accumulation of radiometabolites in brain.

scholarly journals Depiction of microglial activation in aging and dementia: Positron emission tomography with [11C]DPA713 versus [11C](R)PK11195

2016 ◽  
Vol 37 (3) ◽  
pp. 877-889 ◽  
Author(s):  
Masamichi Yokokura ◽  
Tatsuhiro Terada ◽  
Tomoyasu Bunai ◽  
Kyoko Nakaizumi ◽  
Kiyokazu Takebayashi ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Microglial Activation ◽  
Second Generation ◽  
Neuronal Degeneration ◽  
Brain Regions ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Healthy Elderly ◽  
Positron Emission

The presence of activated microglia in the brains of healthy elderly people is a matter of debate. We aimed to clarify the degree of microglial activation in aging and dementia as revealed by different tracers by comparing the binding potential (BPND) in various brain regions using a first-generation translocator protein (TSPO) tracer [11C]( R)PK11195 and a second-generation tracer [11C]DPA713. The BPND levels, estimated using simplified reference tissue models, were compared among healthy young and elderly individuals and patients with Alzheimer’s disease (AD) and were correlated with clinical scores. An analysis of variance showed category-dependent elevation in levels of [11C]DPA713 BPND in all brain regions and showed a significant increase in the AD group, whereas no significant changes among groups were found when [11C]( R)PK11195 BPND was used. Cognito-mnemonic scores were significantly correlated with [11C]DPA713 BPND levels in many brain regions, whereas [11C]( R)PK11195 BPND failed to correlate with the scores. As mentioned elsewhere, the present results confirmed that the second-generation TSPO tracer [11C]DPA713 has a greater sensitivity to TSPO in both aging and neuronal degeneration than [11C]( R)PK11195. Positron emission tomography with [11C]DPA713 is suitable for the delineation of in vivo microglial activation occurring globally over the cerebral cortex irrespective of aging and degeneration.

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