scholarly journals PET imaging of brain aromatase in humans and rhesus monkeys by 11C-labeled cetrozole analogs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kayo Takahashi ◽  
Takamitsu Hosoya ◽  
Kayo Onoe ◽  
Tomoko Mori ◽  
Shusaku Tazawa ◽  
...  
Keyword(s):  
Pet Imaging ◽  
High Specificity ◽  
Binding Potential ◽  
Similar Distribution ◽  
Time Activity ◽  
Brain Functions ◽  
Pet Tracer ◽  
Positron Emission ◽  
Brain Aromatase ◽  
Similar Distribution Pattern

AbstractAromatase is an estrogen synthetic enzyme that plays important roles in brain functions. To quantify aromatase expression in the brain by positron emission tomography (PET), we had previously developed [11C]cetrozole, which showed high specificity and affinity. To develop more efficient PET tracer(s) for aromatase imaging, we synthesized three analogs of cetrozole. We synthesized meta-cetrozole, nitro-cetrozole, and iso-cetrozole, and prepared the corresponding 11C-labeled tracers. The inhibitory activities of these three analogs toward aromatase were evaluated using marmoset placenta, and PET imaging of brain aromatase was performed using the 11C-labeled tracers in monkeys. The most promising analog in the monkey study, iso-cetrozole, was evaluated in the human PET study. The highest to lowest inhibitory activity of the analogs toward aromatase in the microsomal fraction from marmoset placenta was in the following order: iso-cetrozole, nitro-cetrozole, cetrozole, and meta-cetrozole. This order showed good agreement with the order of the binding potential (BP) of each 11C-labeled analog to aromatase in the rhesus monkey brain. A human PET study using [11C]iso-analog showed a similar distribution pattern of binding as that of [11C]cetrozole. The time–activity curves showed that elimination of [11C]iso-cetrozole from brain tissue was faster than that of 11C-cetrozole, indicating more rapid metabolism of [11C]iso-cetrozole. [11C]Cetrozole has preferable metabolic stability for brain aromatase imaging in humans, although [11C]iso-cetrozole might also be useful to measure aromatase level in living human brain because of its high binding potential.

scholarly journals [68Ga]Ga-4HMSA a promising new PET tracer for imaging inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shigufa Kahn Ali ◽  
Samia Ait-Mohand ◽  
Véronique Dumulon-Perreault ◽  
Brigitte Guérin
Keyword(s):  
Pet Imaging ◽  
Experimental Studies ◽  
Production Capacity ◽  
High Specificity ◽  
Upper Body ◽  
Preclinical Model ◽  
Intraplantar Injection ◽  
Pet Tracer ◽  
Positron Emission ◽  
Inflammation Imaging

Abstract Background Imaging diagnosis of inflammation has been challenging for many years. Inflammation imaging agents commonly used in nuclear medicine, such as [67Ga]Ga-citrate and 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) showed some limitations. The identification of a radiotracer with high specificity and low radiation dose is clinically important. With the commercialization of 68Ge/68Ga generators and the high 68Ga cyclotron production capacity, the study of 68Ga-based tracer for inflammation has increased and shown good potential. In the present work, we report the synthesis of 4HMSA, a new acyclic chelator, and its first investigation for 68Ga complexation and as a new positron emission tomography (PET) imaging agent of inflammation in comparison to [68Ga]Ga-citrate. Results The present experimental studies have shown that the novel [68Ga]Ga-4HMSA is stable allowing imaging of inflammation in a preclinical model of adjuvant- and pathogen-based inflammation involving intraplantar injection of complete Freund’s adjuvant (CFA). We also found that [68Ga]Ga-4HMSA displayed similar uptakes in the inflamed paw than [68Ga]Ga-citrate, which are superior compared to those of contralateral (non-injected) paws at days 1–3 from PET imaging. [68Ga]Ga-citrate accumulated in the upper body of the animal such as the liver, lungs and the heart, whereas the [68Ga]Ga-4HMSA revealed low uptakes in the majority of the organs and was cleared relatively rapidly from blood circulation through the kidneys and bladder. Conclusion The results highlight the potential of [68Ga]Ga-4HMSA as an interesting alternative to [68Ga]Ga-citrate for inflammation imaging by PET. The new PET tracer also offers additional advantages than [68Ga]Ga-citrate in term of dosimetry and lower overall background activity.

scholarly journals Dealing with PET radiometabolites

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Krishna Kanta Ghosh ◽  
Parasuraman Padmanabhan ◽  
Chang-Tong Yang ◽  
Sachin Mishra ◽  
Christer Halldin ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Distribution Patterns ◽  
The Body ◽  
Analysis Process ◽  
Pet Tracer ◽  
Positron Emission ◽  
Structural Identity ◽  
Available Technology ◽  
Living Organisms ◽  
Entire Amount

Abstract Positron emission tomography (PET) offers the study of biochemical, physiological, and pharmacological functions at a cellular and molecular level. The performance of a PET study mostly depends on the used radiotracer of interest. However, the development of a novel PET tracer is very difficult, as it is required to fulfill a lot of important criteria. PET radiotracers usually encounter different chemical modifications including redox reaction, hydrolysis, decarboxylation, and various conjugation processes within living organisms. Due to this biotransformation, different chemical entities are produced, and the amount of the parent radiotracer is declined. Consequently, the signal measured by the PET scanner indicates the entire amount of radioactivity deposited in the tissue; however, it does not offer any indication about the chemical disposition of the parent radiotracer itself. From a radiopharmaceutical perspective, it is necessary to quantify the parent radiotracer’s fraction present in the tissue. Hence, the identification of radiometabolites of the radiotracers is vital for PET imaging. There are mainly two reasons for the chemical identification of PET radiometabolites: firstly, to determine the amount of parent radiotracers in plasma, and secondly, to rule out (if a radiometabolite enters the brain) or correct any radiometabolite accumulation in peripheral tissue. Besides, radiometabolite formations of the tracer might be of concern for the PET study, as the radiometabolic products may display considerably contrasting distribution patterns inside the body when compared with the radiotracer itself. Therefore, necessary information is needed about these biochemical transformations to understand the distribution of radioactivity throughout the body. Various published review articles on PET radiometabolites mainly focus on the sample preparation techniques and recently available technology to improve the radiometabolite analysis process. This article essentially summarizes the chemical and structural identity of the radiometabolites of various radiotracers including [11C]PBB3, [11C]flumazenil, [18F]FEPE2I, [11C]PBR28, [11C]MADAM, and (+)[18F]flubatine. Besides, the importance of radiometabolite analysis in PET imaging is also briefly summarized. Moreover, this review also highlights how a slight chemical modification could reduce the formation of radiometabolites, which could interfere with the results of PET imaging. Graphical abstract

Positron Emission Tomography (PET) for Flow Measurement

2011 ◽  
Vol 301-303 ◽  
pp. 1316-1321 ◽  
Author(s):  
Arthur E. Ruggles ◽  
Bi Yao Zhang ◽  
Spero M. Peters
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Three Dimensional ◽  
Bulk Water ◽  
Emission Tomography ◽  
Optical Methods ◽  
Imaging Method ◽  
Analysis And Design ◽  
Pet Tracer ◽  
Positron Emission

Positron Emission Tomography (PET) produces a three dimensional spatial distribution of positron-electron annihilations within an image volume. Various positron emitters are available for use in aqueous, organic and liquid metal flows. Preliminary experiments at the University of Tennessee at Knoxville (UTK) injected small flows of PET tracer into a bulk water flow in a four rod bundle. The trajectory and diffusion of the tracer in the bulk flow were then mapped using a PET scanner. A spatial resolution of 1.4 mm is achieved with current preclinical Micro-PET imaging equipment resulting in 200 MB 3D activity fields. A time resolved 3-D spatial activity profile was also measured. The PET imaging method is especially well suited to complex geometries where traditional optical methods such as LDV and PIV are difficult to apply. PET methods are uniquely useful for imaging in opaque fluids, opaque pressure boundaries, and multiphase studies. Several commercial and shareware Computational Fluid Dynamics (CFD) codes are currently used for science and engineering analysis and design. These codes produce detailed three dimensional flow predictions. The models produced by these codes are often difficult to validate. The development of this experimental technique offers a modality for the comparison of CFD outcomes with experimental data. Developed data sets from PET can be used in verification and validation exercises of simulation outcomes.

scholarly journals PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2289
Author(s):  
Naresh Damuka ◽  
Paul Czoty ◽  
Ashley Davis ◽  
Michael Nader ◽  
Susan Nader ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Neurological Disorders ◽  
Healthy Male ◽  
Time Activity ◽  
Positron Emission ◽  
Pet Ct ◽  
Scan Data ◽  
The Brain ◽  
Human Primate

Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer’s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [11C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [11C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0–120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the “test” and “retest” data. [11C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data (r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [11C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases.

scholarly journals Positron Emission Tomography Imaging Reveals an Importance of Saturable Liver Uptake Transport for the Pharmacokinetics of Metoclopramide

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Fabien Caillé ◽  
Sébastien Goutal ◽  
Solène Marie ◽  
Sylvain Auvity ◽  
Salvatore Cisternino ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Positron Emission Tomography Imaging ◽  
Fold Increase ◽  
Transport Processes ◽  
Emission Tomography ◽  
Liver Uptake ◽  
Time Activity ◽  
Tracer Dose ◽  
Positron Emission

Positron emission tomography (PET) imaging using [11C]metoclopramide, a P-glycoprotein (P-gp) substrate, was used to investigate the contribution of transport processes to metoclopramide liver clearance. The liver kinetics obtained after injection of [11C]metoclopramide were measured using PET in rats (n=4‐5) in the absence (tracer dose) and the presence of a pharmacologic dose of metoclopramide (3 mg/kg), with or without P-gp inhibition using i.v. tariquidar (8 mg/kg). Corresponding [11C]metoclopramide kinetics and metabolism in plasma (n=3) were measured using radio-HPLC analysis. [11C]metoclopramide exposure to the liver and plasma was described by the area under the time-activity curve (AUC) of the radioactivity kinetics in the liver and parent [11C]metoclopramide kinetics in plasma, respectively. The pharmacologic dose of metoclopramide resulted in a ∼2.2-fold increase in [11C]metoclopramide AUCplasma, while P-gp inhibition did not. AUCliver was lower using the pharmacologic dose (42.9 ± 13.8 SUV·min) compared with the tracer dose (210.0 ± 32.4 SUV·min). P-gp inhibition enhanced the liver exposure in the pharmacologic condition only (81.0 ± 3.1 SUV·min). [11C]metoclopramide PET imaging suggests an unpredicted role for hepatocyte uptake transporter(s) in controlling metoclopramide pharmacokinetics in addition to the known contribution of the metabolic enzymes and the P-gp.

scholarly journals A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: Synthesis and preclinical characterization of [18F]SDM-16

2021 ◽  
Author(s):  
Chao Zheng ◽  
Daniel Holden ◽  
Ming-Qiang Zheng ◽  
Richard Pracitto ◽  
Kyle C. Wilcox ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Nonhuman Primate ◽  
Specific Binding ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Time Activity ◽  
Peripheral Tissues ◽  
High Affinity ◽  
Arterial Blood ◽  
Pet Tracer

Purpose: To investigate the synaptic vesicle glycoprotein 2A (SV2A) expression in the whole central nervous system and peripheral tissues, a metabolically stable SV2A radiotracer is desirable to minimize a potential confounding effect of radiometabolites. The aim of this study was to develop and evaluate a metabolically stable SV2A radiotracer, [18F]SDM-16, in nonhuman primate brains. Methods: The racemic SDM-16 (4-(3,5-difluorophenyl)-1-((2-methyl-1H-imidazol-1-yl)methyl)pyrrolidin-2-one ) was synthesized and assayed for in vitro SV2A binding affinity. We synthesized the enantiopure [18F]SDM-16 using the corresponding arylstannane precursor. Nonhuman primate brain PET was performed on a FOCUS 220 system. Arterial blood was drawn for metabolite analysis and construction of plasma input function. Regional time-activity curves (TACs) were evaluated with the one-tissue compartment (1TC) model to obtain the volume of distribution (VT). Binding potential (BPND) was calculated using either the nondisplaceable volume of distribution (VND) or the centrum semiovale (CS) as the reference region. Results: Racemic SDM-16 was synthesized in 3 steps with 44% overall yield and has high affinity (Ki = 3.7 nM) to human SV2A. [18F]SDM-16 was prepared in greater than 99% radiochemical and enantiomeric purity. This radiotracer displayed high specific binding in brain and was metabolically more stable than other SV2A PET tracers. The plasma free fraction (fP) of [18F]SDM-16 was 69%, which was higher than those of [11C]UCB-J (46%), [18F]SynVesT-1 (43%), [18F]SynVesT-2 (41%), and [18F]UCB-H (43%). The TACs were well described with the 1TC. The averaged test-retest variability (TRV) was -9%, and averaged absolute TRV (aTRV) was 10% for all analyzed brain regions. Conclusion: We have successfully synthesized a metabolically stable and high affinity SV2A PET tracer, [18F]SDM-16, which showed high specific and reversible binding in the NHP brain. [18F]SDM-16 may have potential application in the visualization and quantification of SV2A beyond the brain.

scholarly journals A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: Synthesis and preclinical characterization of [18F]SDM-16

2021 ◽  
Author(s):  
Chao Zheng ◽  
Daniel Holden ◽  
Ming-Qiang Zheng ◽  
Richard Pracitto ◽  
Kyle C. Wilcox ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Nonhuman Primate ◽  
Specific Binding ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Time Activity ◽  
Peripheral Tissues ◽  
High Affinity ◽  
Arterial Blood ◽  
Pet Tracer

Abstract PurposeTo investigate the synaptic vesicle glycoprotein 2A (SV2A) expression in the whole central nervous system and peripheral tissues, a metabolically stable SV2A radiotracer is desirable to minimize a potential confounding effect of radiometabolites. The aim of this study was to develop and evaluate a metabolically stable SV2A radiotracer, [18 F]SDM-16, in nonhuman primate brains. MethodsThe racemic SDM-16 (4-(3,5-difluorophenyl)-1-((2-methyl-1H-imidazol-1yl)methyl)pyrrolidin-2-one) was synthesized and assayed for in vitro SV2A binding affinity. We synthesized the enantiopure [18F]SDM-16 using the corresponding arylstannane precursor. Nonhuman primate brain PET was performed on a FOCUS 220 system. Arterial blood was drawn for metabolite analysis and construction of plasma input function. Regional time-activity curves (TACs) were evaluated with the one-tissue compartment (1TC) model to obtain the volume of distribution (VT). Binding potential (BPND) was calculated using either the nondisplaceable volume of distribution (VND) or the centrum semiovale (CS) as the reference region. ResultsRacemic SDM-16 was synthesized in 3 steps with 44% overall yield and has high affinity (K i = 3.7 nM) to human SV2A. [18F]SDM-16 was prepared in greater than 99% radiochemical and enantiomeric purity. This radiotracer displayed high specific binding in brain and was metabolically more stable than other SV2A PET tracers. The plasma free fraction (fP) of [ 18 F]SDM-16 was 69%, which was higher than those of [11C]UCB-J (46%), [18F]SynVesT-1 (43%), [18F]SynVesT-2 (41%), and [18F]UCB-H (43%). The TACs were well described with the 1TC. The averaged test-retest variability (TRV) was -9±8%, and averaged absolute TRV (aTRV) was 10±7% for all analyzed brain regions. ConclusionWe have successfully synthesized a metabolically stable and high affinity SV2A PET tracer, [18F]SDM-16, which showed high specific and reversible binding in the NHP brain. [18F]SDM-16 may have potential application in the visualization and quantification of SV2A beyond the brain.

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 The influence of conditioned stimuli on [11C]-(+)-PHNO PET binding in tobacco smokers after a one week abstinence

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patricia Di Ciano ◽  
Harriet de Wit ◽  
Esmaeil Mansouri ◽  
Sylvain Houle ◽  
Isabelle Boileau ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Preliminary Finding ◽  
Regions Of Interest ◽  
Ventral Pallidum ◽  
Binding Potential ◽  
Brain Areas ◽  
Positron Emission ◽  
Smoking Cues ◽  
Pet Scans ◽  
Larger Sample

AbstractStimuli previously paired with drugs of dependence can produce cravings that are associated with increased dopamine (DA) levels in limbic and striatal brain areas. Positron Emission Tomography (PET) imaging with [11C]-(+)-PHNO allows for a sensitive measurement of changes in DA levels. The purpose of the present study was to investigate changes in DA levels, measured with PET imaging with [11C]-(+)-PHNO, in regions of interest in smokers who had maintained abstinence for 7–10 days. Participants (N = 10) underwent two PET scans on separate days, during which they viewed either smoking-related or neutral images, in counterbalanced order. Craving was measured with the 12-item Tobacco Craving Questionnaire (TCQ) and the Questionnaire on Smoking Urges-Brief (QSU-B). Compared to neutral cues, smoking cues did not increase craving. There were no changes in [11C]-(+)-PHNO binding in the cue condition compared to the neutral condition for most regions of interest (ventral pallidum, globus pallidus, limbic striatum, associative striatum, sensorimotor striatum). However, binding potential in the substantia nigra was greater in the smoking-cue condition, indicating decreased synaptic dopamine. There is a potential change of DA level occurring in midbrain following the presentation of smoking-related cues. However, this preliminary finding would need to be validated with a larger sample.

scholarly journals Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer’s Disease

2021 ◽  
Vol 14 (2) ◽  
pp. 110
Author(s):  
Caitlin Jie ◽  
Valerie Treyer ◽  
Roger Schibli ◽  
Linjing Mu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Second Generation ◽  
Tau Proteins ◽  
Tau Pathology ◽  
Pet Tracer ◽  
Positron Emission ◽  
Tau Pet ◽  
Target Binding

Tauvid has been approved by the U.S. Food and Drug Administration (FDA) in 2020 for positron emission tomography (PET) imaging of adult patients with cognitive impairments undergoing evaluation for Alzheimer’s disease (AD) based on tau pathology. Abnormal aggregation of tau proteins is one of the main pathologies present in AD and is receiving increasing attention as a diagnostic and therapeutic target. In this review, we summarised the production and quality control of Tauvid, its clinical application, pharmacology and pharmacokinetics, as well as its limitation due to off-target binding. Moreover, a brief overview on the second-generation of Tau PET tracers is provided. The approval of Tauvid marks a step forward in the field of AD research and opens up opportunities for second-generation tau tracers to advance tau PET imaging in the clinic.

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