Pharmacokinetic Challenges against Brain Diseases with PET

2014 ◽  
pp. 997-1007
Author(s):  
Hiroshi Watabe ◽  
Keisuke Matsubara ◽  
Yoko Ikoma
Keyword(s):  
High Sensitivity ◽  
Brain Diseases ◽  
Positron Emission ◽  
Functional Images ◽  
Dopamine And Serotonin Receptors ◽  
Anatomical Image ◽  
Time Courses ◽  
Living Organisms ◽  
Types Of Information

Positron emission tomography (PET) is an imaging technology used to visualize distribution of particular ligands inside living organisms. The ligand is labeled by a positron-emitting isotope, such as 11C, 15O, 13N and 18F, and injected into subjects. By detecting ?-rays emitted from the ligand, in vivo biodistribution and kinetics of the ligand can be depicted with high sensitivity. By altering the target ligand for PET, one can see different distributions and time courses of the target. PET provides several biological and functional images inside the body, rather than simply an anatomical image. Therefore, PET can potentially detect biological changes that occur long before anatomical changes begin. PET has been widely used for neuroreceptor and neurotransmitter studies by tracing radioligands, which have selective affinity for a particular site. For example, the dopamine and serotonin receptors are highly related to brain disorders. By analyzing the pharmacokinetics of these ligands using PET, it is possible to noninvasively detect abnormalities in the brain. However, signals from PET contain many different types of information, and it is important to interpret the signals appropriately and choose the proper technique to analyze PET data. This chapter discusses several analytical methods for PET data.

Pharmacokinetic Challenges against Brain Diseases with PET

2011 ◽  
pp. 145-155
Author(s):  
Hiroshi Watabe ◽  
Keisuke Matsubara ◽  
Yoko Ikoma
Keyword(s):  
High Sensitivity ◽  
Brain Diseases ◽  
Positron Emission ◽  
Functional Images ◽  
Dopamine And Serotonin Receptors ◽  
Anatomical Image ◽  
Time Courses ◽  
Living Organisms ◽  
Types Of Information

Positron emission tomography (PET) is an imaging technology used to visualize distribution of particular ligands inside living organisms. The ligand is labeled by a positron-emitting isotope, such as 11C, 15O, 13N and 18F, and injected into subjects. By detecting ?-rays emitted from the ligand, in vivo biodistribution and kinetics of the ligand can be depicted with high sensitivity. By altering the target ligand for PET, one can see different distributions and time courses of the target. PET provides several biological and functional images inside the body, rather than simply an anatomical image. Therefore, PET can potentially detect biological changes that occur long before anatomical changes begin. PET has been widely used for neuroreceptor and neurotransmitter studies by tracing radioligands, which have selective affinity for a particular site. For example, the dopamine and serotonin receptors are highly related to brain disorders. By analyzing the pharmacokinetics of these ligands using PET, it is possible to noninvasively detect abnormalities in the brain. However, signals from PET contain many different types of information, and it is important to interpret the signals appropriately and choose the proper technique to analyze PET data. This chapter discusses several analytical methods for PET data.

Positronium as a biomarker of hypoxia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Paweł Moskal ◽  
Ewa Ł. Stępień
Keyword(s):  
Partial Pressure ◽  
High Sensitivity ◽  
Partial Pressure Of Oxygen ◽  
Physiological Processes ◽  
Positron Emission ◽  
Positronium Lifetime ◽  
Total Body ◽  
Living Organisms ◽  
Cancer Tissues

Abstract In this review article, we present arguments demonstrating that the advent of high sensitivity total-body PET systems and the invention of the method of positronium imaging, open realistic perspectives for the application of positronium as a biomarker for in-vivo assessment of the degree of hypoxia. Hypoxia is a state or condition, in which the availability of oxygen is not sufficient to support physiological processes in tissue and organs. Positronium is a metastable atom formed from electron and positron which is copiously produced in the intramolecular spaces in the living organisms undergoing positron emission tomography (PET). Properties of positronium, such as e.g., lifetime, depend on the size of intramolecular spaces and the concentration in them of oxygen molecules. Therefore, information on the partial pressure of oxygen (pO2) in the tissue may be derived from the positronium lifetime measurement. The partial pressure of oxygen differs between healthy and cancer tissues in the range from 10 to 50 mmHg. Such differences of pO2 result in the change of ortho-positronium lifetime e.g., in water by about 2–7 ps. Thus, the application of positronium as a biomarker of hypoxia requires the determination of the mean positronium lifetime with the resolution in the order of 2 ps. We argue that such resolution is in principle achievable for organ-wise positronium imaging with the total-body PET systems.

scholarly journals Preclinical Molecular Imaging for Precision Medicine in Breast Cancer Mouse Models

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
M. F. Fiordelisi ◽  
L. Auletta ◽  
L. Meomartino ◽  
L. Basso ◽  
G. Fatone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Imaging ◽  
Animal Models ◽  
Early Detection ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Clinical Medicine ◽  
High Sensitivity ◽  
Positron Emission

Precision and personalized medicine is gaining importance in modern clinical medicine, as it aims to improve diagnostic precision and to reduce consequent therapeutic failures. In this regard, prior to use in human trials, animal models can help evaluate novel imaging approaches and therapeutic strategies and can help discover new biomarkers. Breast cancer is the most common malignancy in women worldwide, accounting for 25% of cases of all cancers and is responsible for approximately 500,000 deaths per year. Thus, it is important to identify accurate biomarkers for precise stratification of affected patients and for early detection of responsiveness to the selected therapeutic protocol. This review aims to summarize the latest advancements in preclinical molecular imaging in breast cancer mouse models. Positron emission tomography (PET) imaging remains one of the most common preclinical techniques used to evaluate biomarker expression in vivo, whereas magnetic resonance imaging (MRI), particularly diffusion-weighted (DW) sequences, has been demonstrated as capable of distinguishing responders from nonresponders for both conventional and innovative chemo- and immune-therapies with high sensitivity and in a noninvasive manner. The ability to customize therapies is desirable, as this will enable early detection of diseases and tailoring of treatments to individual patient profiles. Animal models remain irreplaceable in the effort to understand the molecular mechanisms and patterns of oncologic diseases.

Second near-infrared (NIR-II) imaging: a novel diagnostic technique for brain diseases

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Na Xie ◽  
Ya Hou ◽  
Shaohui Wang ◽  
Xiaopeng Ai ◽  
Jinrong Bai ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Tumor ◽  
Near Infrared ◽  
Diagnostic Technique ◽  
High Sensitivity ◽  
Brain Diseases ◽  
Tissue Penetration ◽  
Tumor Inflammation

Abstract Imaging in the second near-infrared II (NIR-II) window, a kind of biomedical imaging technology with characteristics of high sensitivity, high resolution, and real-time imaging, is commonly used in the diagnosis of brain diseases. Compared with the conventional visible light (400–750 nm) and NIR-I (750–900 nm) imaging, the NIR-II has a longer wavelength of 1000–1700 nm. Notably, the superiorities of NIR-II can minimize the light scattering and autofluorescence of biological tissue with the depth of brain tissue penetration up to 7.4 mm. Herein, we summarized the main principles of NIR-II in animal models of traumatic brain injury, cerebrovascular visualization, brain tumor, inflammation, and stroke. Simultaneously, we encapsulated the in vivo process of NIR-II probes and their in vivo and in vitro toxic effects. We further dissected its limitations and following optimization measures.

scholarly journals TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases?

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Bérenger Largeau ◽  
Anne-Claire Dupont ◽  
Denis Guilloteau ◽  
Maria-João Santiago-Ribeiro ◽  
Nicolas Arlicot
Keyword(s):  
Pet Imaging ◽  
Inflammatory Diseases ◽  
Protein A ◽  
Translocator Protein ◽  
Brain Diseases ◽  
Disease Heterogeneity ◽  
Peripheral Tissues ◽  
Positron Emission ◽  
Potential Biomarker

Peripheral sterile inflammatory diseases (PSIDs) are a heterogeneous group of disorders that gathers several chronic insults involving the cardiovascular, respiratory, gastrointestinal, or musculoskeletal system and wherein inflammation is the cornerstone of the pathophysiology. In PSID, timely characterization and localization of inflammatoryfociare crucial for an adequate care for patients. In brain diseases,in vivopositron emission tomography (PET) exploration of inflammation has matured over the last 20 years, through the development of radiopharmaceuticals targeting the translocator protein-18 kDa (TSPO) as molecular biomarkers of activated microglia. Recently, TSPO has been introduced as a possible molecular target for PSIDs PET imaging, making this protein a potential biomarker to address disease heterogeneity, to assist in patient stratification, and to contribute to predicting treatment response. In this review, we summarized the major research advances recently made in the field of TSPO PET imaging in PSIDs. Promising preliminary results have been reported in bowel, cardiovascular, and rheumatic inflammatory diseases, consolidated by preclinical studies. Limitations of TSPO PET imaging in PSIDs, regarding both its large expression in healthy peripheral tissues, unlike in central nervous system, and the production of peripheral radiolabeled metabolites, are also discussed, regarding their possible consequences on TSPO PET signal’s quantification.

scholarly journals Cholinergic Depletion in Alzheimer’s Disease Shown by [18F]FEOBV Autoradiography

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Maxime J. Parent ◽  
Marc-Andre Bedard ◽  
Arturo Aliaga ◽  
Luciano Minuzzi ◽  
Naguib Mechawar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prefrontal Cortex ◽  
Dentate Gyrus ◽  
Postmortem Brain ◽  
Brain Diseases ◽  
Glutamatergic Neurons ◽  
Positron Emission ◽  
Promising Ligand

Rationale. Alzheimer’s Disease (AD) is a neurodegenerative condition characterized in part by deficits in cholinergic basalocortical and septohippocampal pathways. [18F]Fluoroethoxybenzovesamicol ([18F]FEOBV), a Positron Emission Tomography ligand for the vesicular acetylcholine transporter (VAChT), is a potential molecular agent to investigate brain diseases associated with presynaptic cholinergic losses. Purpose. To demonstrate this potential, we carried out an [18F]FEOBV autoradiography study to compare postmortem brain tissues from AD patients to those of age-matched controls. Methods. [18F]FEOBV autoradiography binding, defined as the ratio between regional grey and white matter, was estimated in the hippocampus (13 controls, 8 AD) and prefrontal cortex (13 controls, 11 AD). Results. [18F]FEOBV binding was decreased by 33% in prefrontal cortex, 25% in CA3, and 20% in CA1. No changes were detected in the dentate gyrus of the hippocampus, possibly because of sprouting or upregulation toward the resilient glutamatergic neurons of the dentate gyrus. Conclusion. This is the first demonstration of [18F]FEOBV focal binding changes in cholinergic projections to the cortex and hippocampus in AD. Such cholinergic synaptic (and more specifically VAChT) alterations, in line with the selective basalocortical and septohippocampal cholinergic losses documented in AD, indicate that [18F]FEOBV is indeed a promising ligand to explore cholinergic abnormalities in vivo.

scholarly journals Progress in PET Imaging of Neuroinflammation Targeting COX-2 Enzyme

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3208
Author(s):  
Jaya Prabhakaran ◽  
Andrei Molotkov ◽  
Akiva Mintz ◽  
J. John Mann
Keyword(s):  
Pet Imaging ◽  
Brain Diseases ◽  
Positron Emission ◽  
Disease Staging ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
The Brain ◽  
Lateral Sclerosis

Neuroinflammation and cyclooxygenase-2 (COX-2) upregulation are associated with the pathogenesis of degenerative brain diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), epilepsy, and a response to traumatic brain injury (TBI) or stroke. COX-2 is also induced in acute pain, depression, schizophrenia, various cancers, arthritis and in acute allograft rejection. Positron emission tomography (PET) imaging allows for the direct measurement of in vivo COX-2 upregulation and thereby enables disease staging, therapy evaluation and aid quantifying target occupancy of novel nonsteroidal anti-inflammatory drugs or NSAIDs. Thus far, no clinically useful radioligand is established for monitoring COX-2 induction in brain diseases due to the delay in identifying qualified COX-2-selective inhibitors entering the brain. This review examines radiolabeled COX-2 inhibitors reported in the past decade and identifies the most promising radioligands for development as clinically useful PET radioligands. Among the radioligands reported so far, the three tracers that show potential for clinical translation are, [11CTMI], [11C]MC1 and [18F]MTP. These radioligands demonstrated BBB permeablity and in vivo binding to constitutive COX-2 in the brain or induced COX-2 during neuroinflammation.

scholarly journals Sodium [18F]Fluoride PET Can Efficiently Monitor In Vivo Atherosclerotic Plaque Calcification Progression and Treatment

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 275
Author(s):  
Alexandru Florea ◽  
Julius P. Sigl ◽  
Agnieszka Morgenroth ◽  
Andreas Vogg ◽  
Sabri Sahnoun ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vitamin K ◽  
Early Stage ◽  
Small Animal ◽  
High Sensitivity ◽  
Chow Diet ◽  
Beneficial Effects ◽  
Positron Emission ◽  
18F Fluoride

Given the high sensitivity and specificity of sodium [18F]Fluoride (Na[18F]F) for vascular calcifications and positive emerging data of vitamin K on vascular health, the aim of this study is to assess the ability of Na[18F]F to monitor therapy and disease progression in a unitary atherosclerotic mouse model. ApoE−/− mice were placed on a Western-type diet for 12-weeks and then split into four groups. The early stage atherosclerosis group received a chow diet for an additional 12-weeks, while the advanced atherosclerosis group continued the Western-type diet. The Menaquinone-7 (MK-7) and Warfarin groups received MK-7 or Warfarin supplementation during the additional 12-weeks, respectively. Control wild type mice were fed a chow diet for 24-weeks. All of the mice were scanned with Na[18F]F using a small animal positron emission tomography (PET)/computed tomography (CT). The Warfarin group presented spotty calcifications on the CT in the proximal aorta. All of the spots corresponded to dense mineralisations on the von Kossa staining. After the control, the MK-7 group had the lowest Na[18F]F uptake. The advanced and Warfarin groups presented the highest uptake in the aortic arch and left ventricle. The advanced stage group did not develop spotty calcifications, however Na[18F]F uptake was still observed, suggesting the presence of micro-calcifications. In a newly applied mouse model, developing spotty calcifications on CT exclusively in the proximal aorta, Na[18F]F seems to efficiently monitor plaque progression and the beneficial effects of vitamin K on cardiovascular disease.

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

Click Chemistry Expedited Radiosynthesis: Sulfur [18F]fluoride Exchange of Aryl Fluorosulfates

2019 ◽  
Author(s):  
Qinheng Zheng ◽  
Hongtao Xu ◽  
Hua Wang ◽  
Wen-Ge Han Du ◽  
Nan Wang ◽  
...  
Keyword(s):  
Click Chemistry ◽  
High Performance ◽  
Isotopic Exchange ◽  
Tumor Imaging ◽  
Radiochemical Yield ◽  
Exchange Method ◽  
Molar Activity ◽  
Positron Emission ◽  
Sulfur Fluoride

The lack of simple, efficient [<sup>18</sup>F]fluorination processes and new target-specific organofluorine probes remains the major challenge of fluorine-18-based positron emission tomography (PET). We report here a fast isotopic exchange method for the radiosynthesis of aryl [<sup>18</sup>F]fluorosulfate based PET agents enabled by the emerging sulfur fluoride exchange (SuFEx) click chemistry. The method has been applied to the fully-automated <sup>18</sup>F-radiolabeling of twenty-five structurally diverse aryl fluorosulfates with excellent radiochemical yield (83–100%) and high molar activity (up to 281 GBq µmol<sup>–1</sup>) at room temperature in 30 seconds. The purification of radiotracers requires no time-consuming high-performance liquid chromatography (HPLC), but rather a simple cartridge filtration. The utility of aryl [<sup>18</sup>F]fluorosulfate is demonstrated by the <i>in vivo</i> tumor imaging by targeting poly(ADP-ribose) polymerase 1 (PARP1).

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