scholarly journals Tracer Kinetic Modeling of [11C]AFM, a New PET Imaging Agent for the Serotonin Transporter

2013 ◽  
Vol 33 (12) ◽  
pp. 1886-1896 ◽  
Author(s):  
Mika Naganawa ◽  
Nabeel Nabulsi ◽  
Beata Planeta ◽  
Jean-Dominique Gallezot ◽  
Shu-Fei Lin ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Serotonin Transporter ◽  
Emission Tomography ◽  
Binding Potential ◽  
Reference Tissue ◽  
Time Activity ◽  
Tissue Model ◽  
Positron Emission ◽  
Arterial Input Functions ◽  
Tissue Models

[11C]AFM, or [11C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine, is a new positron emission tomography (PET) radioligand with high affinity and selectivity for the serotonin transporter (SERT). The purpose of this study was to determine the most appropriate kinetic model to quantify [11C]AFM binding in the healthy human brain. Positron emission tomography data and arterial input functions were acquired from 10 subjects. Compartmental modeling and the multilinear analysis-1(MA1) method were tested using the arterial input functions. The one-tissue model showed a lack of fit in low-binding regions, and the two-tissue model failed to estimate parameters reliably. Regional time–activity curves were well described by MA1. The rank order of [11C]AFM binding potential ( BPND) matched well with the known regional SERT densities. For routine use of [11C]AFM, several noninvasive methods for quantification of regional binding were evaluated, including simplified reference tissue models (SRTM and SRTM2), and multilinear reference tissue models (MRTM and MRTM2). The best methods for region of interest (ROI) analysis were MA1, MRTM2, and SRTM2, with fixed population kinetic values ( k′2 or b′) for the reference methods. The MA1 and MRTM2 methods were best for parametric imaging. These results showed that [11C]AFM is a suitable PET radioligand to image and quantify SERT in humans.

scholarly journals Kinetic Modeling of the Serotonin 5-HT1B Receptor Radioligand [11C]P943 in Humans

2009 ◽  
Vol 30 (1) ◽  
pp. 196-210 ◽  
Author(s):  
Jean-Dominique Gallezot ◽  
Nabeel Nabulsi ◽  
Alexander Neumeister ◽  
Beata Planeta-Wilson ◽  
Wendol A Williams ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Arterial Input Function ◽  
Human Subjects ◽  
Emission Tomography ◽  
Binding Potential ◽  
Noninvasive Methods ◽  
Reference Tissue ◽  
Positron Emission ◽  
Tissue Models

[11C]P943 is a new radioligand recently developed to image and quantify serotonin 5-Hydroxytryptamine (5-HT1B) receptors with positron emission tomography (PET). The purpose of this study was to evaluate [11C]P943 for this application in humans, and to determine the most suitable quantification method. Positron emission tomography data and arterial input function measurements were acquired in a cohort of 32 human subjects. Using arterial input functions, compartmental modeling, the Logan graphical analysis, and the multilinear method MA1 were tested. Both the two tissue-compartment model and MA1 provided good fits of the PET data and reliable distribution volume estimates. Using the cerebellum as a reference region, BPND binding potential estimates were computed. [11C]P943 BPND estimates were significantly correlated with in vitro measurements of the density of 5-HT1B receptors, with highest values in the occipital cortex and pallidum. To evaluate noninvasive methods, two- and three-parameter graphical analyses, Simplified Reference Tissue Models (SRTM and SRTM2), and Multilinear Reference Tissue Models (MRTM and MRTM2) were tested. The MRTM2 model provided the best correlation with MA1 binding-potential estimates. Parametric images of the volume of distribution or binding potential of [11C]P943 could be computed using both MA1 and MRTM2. The results show that [11C]P943 provides quantitative measurements of 5-HT1B binding potential.

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 Positron Emission Tomography Quantification of [11C]-DASB Binding to the Human Serotonin Transporter: Modeling Strategies

2001 ◽  
Vol 21 (11) ◽  
pp. 1342-1353 ◽  
Author(s):  
Nathalie Ginovart ◽  
Alan A. Wilson ◽  
Jeffrey H. Meyer ◽  
Doug Hussey ◽  
Sylvain Houle
Keyword(s):  
Positron Emission Tomography ◽  
Serotonin Transporter ◽  
Quantitative Methods ◽  
Goodness Of Fit ◽  
Emission Tomography ◽  
Binding Potential ◽  
Reference Region ◽  
Time Activity ◽  
Healthy Humans ◽  
Positron Emission

[11C]-DASB, namely [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile, is a new highly selective radioligand for the in vivo visualization of the serotonin transporter (SERT) using positron emission tomography (PET). The current study evaluates different kinetic modeling strategies for quantification of [11C]-DASB binding in five healthy humans. Kinetic analyses of tissue data were performed with a one-tissue (1CM) and a two-tissue (2CM) compartment model. Time-activity curves were well described by a 1CM for all regions. A 2CM model with four parameters failed to converge reliably. Reliable fits of the data were obtained only if no more than three parameters were allowed to vary. However, even then, the rate constants k3 and k4 were estimated with poor precision. Only the ratio k3/k4 was stable. Goodness of fit was not improved by using a 2CM as compared with a 1CM. The minimal study duration required to obtain stable k3/k4 estimates was 80 minutes. For routine use of [11C]-DASB, several simplified methods using the cerebellum as a reference region to estimate nonspecific binding were also evaluated. The transient equilibrium, the linear graphical analysis, the ratio of target to reference region, and the simplified reference tissue methods all gave binding potential values consistent with those obtained with the 2CM. The suitability of [11C]-DASB for research on the SERT using PET is thus supported by the observations that tissue data can be described using a kinetic analysis and that simplified quantitative methods, using the cerebellum as reference, provide reliable estimates of SERT binding parameters.

scholarly journals Temperament, character and serotonin activity in the human brain: a positron emission tomography study based on a general population cohort

2012 ◽  
Vol 43 (4) ◽  
pp. 881-894 ◽  
Author(s):  
L. Tuominen ◽  
J. Salo ◽  
J. Hirvonen ◽  
K. Någren ◽  
P. Laine ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Serotonin Transporter ◽  
Population Based ◽  
Emission Tomography ◽  
Brain Serotonin ◽  
Binding Potential ◽  
Positron Emission ◽  
General Population Cohort ◽  
Temperament Dimension

BackgroundThe psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension ‘harm avoidance’ (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT) density in vivo with positron emission tomography (PET) in healthy individuals with high or low HA scores using an ‘oversampling’ study design.MethodSubjects consistently in either upper or lower quartiles for the HA trait were selected from a population-based cohort in Finland (n = 2075) with pre-existing Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of psychiatric and somatic disorders were included in the matched high- and low-HA groups. The main outcome measure was regional 5-HTT binding potential (BPND) in high- and low-HA groups estimated with PET and [11C]N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine ([11C]MADAM). In secondary analyses, 5-HTT BPND was correlated with other TCI dimensions.Results5-HTT BPND did not differ between high- and low-HA groups in the midbrain or any other brain region. This result remained the same even after adjusting for other relevant TCI dimensions. Higher 5-HTT BPND in the raphe nucleus predicted higher scores in ‘self-directedness’.ConclusionsThis study does not support an association between the temperament dimension HA and serotonin transporter density in healthy subjects. However, we found a link between high serotonin transporter density and high ‘self-directedness’ (ability to adapt and control one's behaviour to fit situations in accord with chosen goals and values). We suggest that biological factors are more important in explaining variability in character than previously thought.

scholarly journals Serotonin 5HT2 Receptor Imaging in the Human Brain Using Positron Emission Tomography and a New Radioligand, [18F]Altanserin: Results in Young Normal Controls

1995 ◽  
Vol 15 (5) ◽  
pp. 787-797 ◽  
Author(s):  
B. Sadzot ◽  
C. Lemaire ◽  
P. Maquet ◽  
E. Salmon ◽  
A. Plenevaux ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
High Specific Activity ◽  
Emission Tomography ◽  
Binding Potential ◽  
Receptor Imaging ◽  
Time Activity ◽  
Arterial Blood ◽  
Positron Emission

Changes in serotonin-2 receptors have been demonstrated in brain autopsy material from patients with various neurodegenerative and affective disorders. It would be desirable to locate a ligand for the study of these receptors in vivo with positron emission tomography (PET). Altanserin is a 4-benzoylpiperidine derivative with a high affinity and selectivity for S2 receptors in vitro. Dynamic PET studies were carried out in nine normal volunteers with high-specific activity (376–1,680 mCi/μmol) [18F]altanserin. Arterial blood samples were obtained and the plasma time–activity curves were corrected for the presence of labeled metabolites. Thirty minutes after injection, selective retention of the radioligand was observed in cortical areas, while the cerebellum, caudate, and thalamus had low radioactivity levels. Specific binding reached a plateau between 30 and 65 min postinjection at 1.8% of the injected dose/L of brain and then decreased, indicating the reversibility of the binding. The total/nonspecific binding ratio reached 2.6 for times between 50 and 70 min postinjection. The graphical analysis proposed by Logan et al. allowed us to estimate the binding potential ( Bmax/ KD). Pretreatment with ketanserin was given to three volunteers and brain activity remained uniformly low. An additional study in one volunteer showed that [18F]altanserin can be displaced from the receptors by large doses of ketanserin. At the end of the study, unchanged altanserin was 57% of the total plasma activity. These results suggest that [18F]altanserin is selective for S2 receptors in vivo as it is in vitro. They indicate that [18F]altanserin is suitable for imaging and quantifying S2 receptors with PET in humans.

scholarly journals Reproducibility of Striatal and Thalamic Dopamine D2 Receptor Binding Using [11C]raclopride with High-Resolution Positron Emission Tomography

2010 ◽  
Vol 31 (1) ◽  
pp. 155-165 ◽  
Author(s):  
Kati Alakurtti ◽  
Sargo Aalto ◽  
Jarkko J Johansson ◽  
Kjell Någren ◽  
Terhi Tuokkola ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
High Resolution ◽  
Spatial Resolution ◽  
Receptor Binding ◽  
Dopamine D2 Receptor ◽  
Intraclass Correlation ◽  
Emission Tomography ◽  
Binding Potential ◽  
Reference Tissue ◽  
Positron Emission

Positron emission tomography (PET) imaging of small striatal brain structures such as the ventral striatum (VST) has been hampered by low spatial resolution causing partial-volume effects. The high-resolution research tomograph (HRRT) is a brain-dedicated PET scanner that has considerably better spatial resolution than its predecessors. However, its superior spatial resolution is associated with a lower signal-to-noise ratio. We evaluated the test–retest reliability of the striatal and thalamic dopamine D2 receptor binding using the HRRT scanner. Seven healthy male volunteers underwent two [11C]raclopride PET scans with a 2.5-hour interval. Dopamine D2 receptor availability was quantified as binding potential (BPND) using the simplified reference tissue model. To evaluate the reproducibility of repeated BPND estimations, absolute variability (VAR) and intraclass correlation coefficients (ICCs) were calculated. VAR values indicated fairly good reproducibility and were 3.6% to 4.5% for the caudate nucleus and putamen and 4.5% to 6.4% for the lateral and medial part of the thalamus. In the VST, the VAR value was 5.8% when the definition was made in the coronal plane. However, the ICC values were only moderate, in the range of 0.34 to 0.66, for all regions except the putamen (0.87). Experimental signal processing methods improved neither ICC nor VAR values significantly.

scholarly journals Validation and Quantification of [18F]Altanserin Binding in the Rat Brain Using Blood Input and Reference Tissue Modeling

2011 ◽  
Vol 31 (12) ◽  
pp. 2334-2342 ◽  
Author(s):  
Patrick J Riss ◽  
Young T Hong ◽  
David Williamson ◽  
Daniele Caprioli ◽  
Sergey Sitnikov ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Brain Uptake ◽  
Reference Tissue ◽  
Tissue Modeling ◽  
Validation And Quantification ◽  
Positron Emission ◽  
Significant Uptake ◽  
Tissue Models ◽  
The Brain

The 5-hydroxytryptamine type 2a (5-HT2A) selective radiotracer [18F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats. Metabolite-corrected plasma input modeling was compared with reference tissue modeling using the cerebellum as reference tissue. [18F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT2A receptors. Full binding saturation and displacement was documented, and no significant uptake of radioactive metabolites was detected in the brain. Blood input as well as reference tissue models were equally appropriate to describe the radiotracer kinetics. [18F]altanserin is suitable for quantification of 5-HT2A receptor availability in rats.

scholarly journals Evaluation of Four Pyridine Analogs to Characterize 6-OHDA-Induced Modulation of mGluR5 Function in Rat Brain Using microPET Studies

2007 ◽  
Vol 27 (9) ◽  
pp. 1623-1631 ◽  
Author(s):  
Aijun Zhu ◽  
Xukui Wang ◽  
Meixiang Yu ◽  
Ji-Quan Wang ◽  
Anna-Liisa Brownell
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Emission Tomography ◽  
Binding Potential ◽  
Sprague Dawley ◽  
Imaging Studies ◽  
Reference Tissue ◽  
Positron Emission ◽  
The Right

Micro-positron emission tomography imaging studies were conducted to characterize modulation of metabotropic glutamate subtype-5 receptor (mGluR5) function in a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease using four analogical PET ligands: 2-[11C]methyl-6-(2-phenylethynyl) pyridine ([11C]MPEP), 2-(2-(3-[11C]methoxyphenyl)ethynyl)pyridine ([11C]M-MPEP), 2-(2-(5-[11C]methoxypyridin-3-yl)ethynyl)pyridine ([11C]M-PEPy), and 3-[(2-[18F]methyl-1,3-thiazol-4-yl)ethynyl]pyridine ([18F]M-TEP). A total of 45 positron emission tomography (PET) imaging studies were conducted on nine male Sprague-Dawley rats within 4 to 6 weeks after unilateral 6-OHDA lesioning into the right medial forebrain bundle. The severity of the lesion was determined with [11C]CFT ([11C]2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane), a specific and sensitive ligand for imaging dopamine transporter function. The binding potential (BP) images were processed on pixel-by-pixel basis by using a method of the distribution volume ratio with cerebellum as a reference tissue. The values for BP were determined on striatum, hippocampus, and cortex. [11C]CFT binding was decreased on the lesioned (right) striatum by 35.4% ± 13.4% compared with the intact left striatum, indicating corresponding loss of presynaptic dopamine terminals. On the same areas of the lesioned striatum, three of the four tested mGluR5 ligands showed enhanced binding characteristics. The average differences between the right and left striatum were 4.4% ± 6.5% ( P < 0.05) with [11C]MPEP, 0.1% ± 1.7% ( P > 0.05) with [11C]M-MPEP, 3.9% ± 4.6% ( P < 0.05) with [11C]M-PEPy, and 6.6% ± 2.7% ( P > 0.05) with [18F]M-TEP. The enhanced binding was also observed in the right hippocampus and cortex. These studies showed that glutamatergic neurotransmission might have a complementary role in dopaminergic degeneration, which can be evaluated by in vivo PET imaging.

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