Synthesis of high specific activity 6-[18F]fluorodopamine for positron emission tomography studies of sympathetic nervous tissue

1991 ◽  
Vol 34 (2) ◽  
pp. 861-863 ◽  
Author(s):  
Yu Shin Ding ◽  
Joanna S. Fowler ◽  
S. John Gatley ◽  
Stephen L. Dewey ◽  
Alfred P. Wolf ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Nervous Tissue ◽  
Specific Activity ◽  
High Specific Activity ◽  
Emission Tomography ◽  
Positron Emission ◽  
Sympathetic Nervous

scholarly journals Quantification of δ-Opioid Receptors in Human Brain with N1′ -([11C]Methyl) Naltrindole and Positron Emission Tomography

1999 ◽  
Vol 19 (9) ◽  
pp. 956-966 ◽  
Author(s):  
Justin S. Smith ◽  
Jon-Kar Zubieta ◽  
Julie C. Price ◽  
John E. Flesher ◽  
Igal Madar ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Opioid Receptors ◽  
Receptor Binding ◽  
Specific Activity ◽  
High Specific Activity ◽  
Emission Tomography ◽  
Opioid Antagonist ◽  
Tracer Transport ◽  
Positron Emission

The regional binding of N1′ -([11C]methyl)naltrindole (MeNTI), a selective δ-opioid antagonist, was studied in healthy human subjects with positron emission tomography (PET). After the bolus intravenous administration of high specific activity [11C]MeNTI, PET was performed over 90 minutes. Arterial plasma samples were obtained during the scanning period and assayed for the presence of radiolabeled metabolites. The data were analyzed with various kinetic (two-and three-compartment models, Patlak graphical analysis) and nonkinetic (apparent volume of distribution and activity at a late scanning time) approaches. This tracer showed irreversible binding characteristics during the scanning period used. The results of the analyses also were compared with the density and distribution of δ-opioid receptors in the human brain in vitro. Additionally, computer simulations were performed to assess the effects of changes in receptor binding and tracer transport changes on the perceived binding parameters obtained with the models. A constrained three-compartment kinetic model was demonstrated to be superior to other quantification models for the description of MeNTI kinetics and quantification of δ receptor binding in the human brain with 11C-labeled MeNTI.

Radiochlorine: an underutilized halogen tool

2019 ◽  
Vol 107 (9-11) ◽  
pp. 1027-1031 ◽  
Author(s):  
Suzanne E. Lapi ◽  
Jonathan W. Engle
Keyword(s):  
Specific Activity ◽  
Research Effort ◽  
High Specific Activity ◽  
Low Energy ◽  
Emission Tomography ◽  
Clinical Settings ◽  
Cyclotron Production ◽  
Positron Emission ◽  
Chemistry Development ◽  
Fundamental Research

Abstract Halogen radioisotopes have a variety of physical half-lives which are suitable for probing a wide variety of pharmacokinetic processes. Compared with other radiohalogens, relatively little work has been done with radiochlorine. However, high specific activity radioisotopes of chlorine are available from low energy cyclotron production in quantities suitable for positron emission tomography (PET) and fundamental research. In particular, the sole radioisotope of chlorine which may be used for PET imaging, 34mCl, has achieved a state of development that permits imaging in clinical settings though sparse research effort has been focused on this isotope over the last 40 years. Additionally, the other longer-lived radioisotopes of chlorine will likely continue to show utility for more traditional radiotracer studies and chemistry development.

scholarly journals Measurement of Benzodiazepine Receptor Number and Affinity in Humans Using Tracer Kinetic Modeling, Positron Emission Tomography, and [11C]Flumazenil

1993 ◽  
Vol 13 (4) ◽  
pp. 656-667 ◽  
Author(s):  
Julie C. Price ◽  
Helen S. Mayberg ◽  
Robert F. Dannals ◽  
Alan A. Wilson ◽  
Hayden T. Ravert ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Specific Activity ◽  
Free Fraction ◽  
Benzodiazepine Receptor ◽  
Occipital Cortex ◽  
Compartment Model ◽  
Brain Regions ◽  
Emission Tomography ◽  
Positron Emission ◽  
Convergence Problems

Kinetic methods were used to obtain regional estimates of benzodiazepine receptor concentration ( Bmax) and equilibrium dissociation constant ( Kd) from high and low specific activity (SA) [11C]flumazenil ([11C] Ro 15-1788) positron emission tomography studies of five normal volunteers. The high and low SA data were simultaneously fit to linear and nonlinear three-compartment models, respectively. An additional inhibition study (pretreatment with 0.15 mg/kg of flumazenil) was performed on one of the volunteers, which resulted in an average gray matter K1/ k2 estimate of 0.68 ± 0.08 ml/ml (linear three-compartment model, nine brain regions). The free fraction of flumazenil in plasma ( f1) was determined for each study (high SA f1: 0.50 ± 0.03; low SA f1: 0.48 ± 0.05). The free fraction in brain ( f2) was calculated using the inhibition K1/ k2 ratio and each volunteer's mean f1 value ( f2 across volunteers = 0.72 ± 0.03 ml/ml). Three methods (Methods I–III) were examined. Method I determined five kinetic parameters simultaneously [ K1, k2, k3 (= kon f2 Bmax), k4, and kon f2/SA] with no a priori constraints. An average kon value of 0.030 ± 0.003 n M−1 min−1 was estimated for receptor-rich regions using Method I. In Methods II and III, the kon f2/SA parameter was specifically constrained using the Method I value of kon and the volunteer's values of f2 and low SA (Ci/μmol). Four parameters were determined simultaneously using Method II. In Method III, K1/ k2 was fixed to the inhibition value and only three parameters were estimated. Method I provided the most variable results and convergence problems for regions with low receptor binding. Method II provided results that were less variable but very similar to the Method I results, without convergence problems. However, the K1/ k2 ratios obtained by Method II ranged from 1.07 in the occipital cortex to 0.61 in the thalamus. Fixing the K1/ k2 ratio in Method III provided a method that was physiologically consistent with the fixed value of f2 and resulted in parameters with considerably lower variability. The average Bmax values obtained using Method III were 100 ± 25 n M in the occipital cortex, 64 ±18 n M in the cerebellum, and 38 ± 5.5 n M in the thalamus; the average Kd was 8.9 ± 1.0 n M (five brain regions).

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 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 Quantification of Human Opiate Receptor Concentration and Affinity Using High and Low Specific Activity [11C]Diprenorphine and Positron Emission Tomography

1991 ◽  
Vol 11 (2) ◽  
pp. 204-219 ◽  
Author(s):  
Bernard Sadzot ◽  
Julie C. Price ◽  
Helen S. Mayberg ◽  
Kenneth H. Douglass ◽  
Robert F. Dannals ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Specific Activity ◽  
Free Fraction ◽  
Receptor Occupancy ◽  
Occipital Cortex ◽  
Opiate Receptor ◽  
Emission Tomography ◽  
Positron Emission ◽  
Receptor Concentration ◽  
The Brain

[11C]Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration ( Bmax) and affinity ( Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769–5,920 Ci/mmol) and low (27–80 Ci/mmol) specific activity (SA) [11C]diprenorphine. Two subjects were studied a third time using high SA [11C]diprenorphine after a pretreatment with 1–1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/ k4 ratio varied from 1.0 ± 0.2 (occipital cortex) to 8.6 ± 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the kon f2 product. The measured free fraction of [11C]diprenorphine in plasma ( f1) was 0.30 ± 0.03, the average K1/ k2 ratio from the two naloxone studies was 1.1 ± 0.2, and the calculated free fraction of [11C]diprenorphine in the brain ( f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 ± 0.5 (occipital cortex) to 20.6 ± 7.3 (cingulate cortex) n M. The average Kd (eight brain regions) was 0.85 ± 0.17 n M.

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