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Diabetes/metabolism Research and Reviews Jan 2023Approximately 30% of the global population is affected by obesity. Traditional non-surgical measures for weight loss have limited efficacy and tolerability. Therefore,... (Review)
Review
BACKGROUND
Approximately 30% of the global population is affected by obesity. Traditional non-surgical measures for weight loss have limited efficacy and tolerability. Therefore, there is a need for novel, effective therapies. Brown adipose tissue (BAT) has been implicated in physiological energy expenditure, indicating that it could be targeted to achieve weight loss in humans. The use of F-fluorodeoxyglucose ( F-FDG) positron emission tomography-computed tomography-(PET-CT) imaging has enabled the discovery of functionally active BAT in the supraclavicular, subclavian, and thoracic spine regions of human adults. This review aims to discuss the reasons behind the renewed interest in BAT, assess whether it is metabolically important in humans, and evaluate its feasibility as a therapeutic target for treating obesity.
SOURCES OF MATERIAL
PubMed Central, Europe PMC, Medline.
FINDINGS
In vivo studies have shown that BAT activity is regulated by thyroid hormones and the sympathetic nervous system. Furthermore, BAT uniquely contains uncoupling protein 1 (UCP1) that is largely responsible for non-shivering thermogenesis. Cold exposure can increase BAT recruitment through the browning of white adipose tissue (WAT); however, this technique has practical limitations that may preclude its use. Currently available medicines for humans, such as the β3-adrenergic receptor agonist mirabegron or the farnesoid X receptor agonist obeticholic acid, have generated excitement, although adverse effects are a concern. Capsinoids represent a tolerable alternative, which require further investigation.
CONCLUSIONS
The use of currently available BAT-activating agents alone is unlikely to achieve significant weight loss in humans. A combination of BAT activation with physical exercise and modern, successful dietary strategies represents a more realistic option.
Topics: Adult; Humans; Adipose Tissue, Brown; Positron Emission Tomography Computed Tomography; Body Weight; Obesity; Fluorodeoxyglucose F18; Weight Loss; Adipose Tissue, White
PubMed: 36398906
DOI: 10.1002/dmrr.3594 -
Neuroscience Oct 2021Altered brain metabolism contributes to pathophysiology in cerebrovascular and neurodegenerative diseases such as stroke and Alzheimer's disease. Current clinical tools... (Review)
Review
Altered brain metabolism contributes to pathophysiology in cerebrovascular and neurodegenerative diseases such as stroke and Alzheimer's disease. Current clinical tools to study brain metabolism rely on positron emission tomography (PET) requiring specific hardware and radiotracers, or magnetic resonance spectroscopy (MRS) involving technical complexity. In this review we highlight deuterium metabolic imaging (DMI) as a novel translational technique for assessment of brain metabolism, with examples from brain tumor and stroke studies. DMI is an MRS-based method that enables detection of deuterated substrates, such as glucose, and their metabolic products, such as lactate, glutamate and glutamine. It provides additional detail of downstream metabolites compared to analogous approaches like fluorodeoxyglucose (FDG)-PET, and can be implemented and executed on clinical and preclinical MR systems. We foresee that DMI, with future improvements in spatial and temporal resolutions, holds promise to become a valuable MR imaging (MRI) method for non-invasive mapping of glucose uptake and its downstream metabolites in healthy and diseased brain.
Topics: Brain; Deuterium; Fluorodeoxyglucose F18; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Positron-Emission Tomography
PubMed: 33493618
DOI: 10.1016/j.neuroscience.2021.01.023 -
Chemical Society Reviews Jun 2023Carbohydrate diversity is foundational in the molecular literacy that regulates cellular function and communication. Consequently, delineating and leveraging this... (Review)
Review
Carbohydrate diversity is foundational in the molecular literacy that regulates cellular function and communication. Consequently, delineating and leveraging this structure-function interplay continues to be a core research objective in the development of candidates for biomedical diagnostics. A totemic example is the ubiquity of 2-deoxy-2-[F]-fluoro-D-glucose (2-[F]-FDG) as a radiotracer for positron emission tomography (PET), in which metabolic trapping is harnessed. Building on this clinical success, more complex sugars with unique selectivities are gaining momentum in molecular recognition and personalised medicine: this reflects the opportunities that carbohydrate-specific targeting affords in a broader sense. In this Tutorial Review, key milestones in the development of 2-[F]-FDG and related glycan-based radiotracers for PET are described, with their diagnostic functions, to assist in navigating this rapidly expanding field of interdisciplinary research.
Topics: Fluorodeoxyglucose F18; Radiopharmaceuticals; Positron-Emission Tomography; Carbohydrates; Glucose
PubMed: 37171037
DOI: 10.1039/d3cs00037k -
Seminars in Nuclear Medicine Nov 2021White blood cells activated by either a pathogen or as part of a systemic inflammatory disease are characterized by high energy consumption and are therefore taking up... (Review)
Review
White blood cells activated by either a pathogen or as part of a systemic inflammatory disease are characterized by high energy consumption and are therefore taking up the glucose analogue PET tracer FDG avidly. It is therefore not surprising that a steadily growing body of research and clinical reports now supports the use of FDG PET/CT to diagnose a wide range of patients with non-oncological diseases. However, using FDG PET/CT in patients with infectious or inflammatory diseases has some limitations and potential pitfalls that are not necessarily as pronounced in oncology FDG PET/CT. Some of these limitations are of a general nature and related to the laborious acquisition of PET images in patients that are often acutely ill, whereas others are more disease-specific and related to the particular metabolism in some of the organs most commonly affected by infections or inflammatory disease. Both inflammatory and infectious diseases are characterized by a more diffuse and less pathognomonic pattern of FDG uptake than oncology FDG PET/CT and the affected organs also typically have some physiological FDG uptake. In addition, patients referred to PET/CT with suspected infection or inflammation are rarely treatment naïve and may have received varying doses of antibiotics, corticosteroids or other immune-modulating drugs at the time of their examination. Combined, this results in a higher rate of false positive FDG findings and also in some cases a lower sensitivity to detect active disease. In this review, we therefore discuss the limitations and pitfalls of FDG PET/CT to diagnose infections and inflammation taking these issues into consideration. Our review encompasses the most commonly encountered inflammatory and infectious diseases in head and neck, in the cardiovascular system, in the abdominal organs and in the musculoskeletal system. Finally, new developments in the field of PET/CT that may help overcome some of these limitations are briefly highlighted.
Topics: Fluorodeoxyglucose F18; Humans; Inflammation; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography
PubMed: 34246448
DOI: 10.1053/j.semnuclmed.2021.06.008 -
Pediatric Radiology Feb 2022Accurate staging and re-staging of cancer in children is crucial for patient management. Currently, children with a newly diagnosed cancer must undergo a series of... (Review)
Review
Accurate staging and re-staging of cancer in children is crucial for patient management. Currently, children with a newly diagnosed cancer must undergo a series of imaging tests, which are stressful, time-consuming, partially redundant, expensive, and can require repetitive anesthesia. New approaches for pediatric cancer staging can evaluate the primary tumor and metastases in a single session. However, traditional one-stop imaging tests, such as CT and positron emission tomography (PET)/CT, are associated with considerable radiation exposure. This is particularly concerning for children because they are more sensitive to ionizing radiation than adults and they live long enough to experience secondary cancers later in life. In this review article we discuss child-tailored imaging tests for tumor detection and therapy response assessment - tests that can be obtained with substantially reduced radiation exposure compared to traditional CT and PET/CT scans. This includes diffusion-weighted imaging (DWI)/MRI and integrated [F-18]2-fluoro-2-deoxyglucose (F-FDG) PET/MRI scans. While several investigators have compared the value of DWI/MRI and F-FDG PET/MRI for staging pediatric cancer, the value of these novel imaging technologies for cancer therapy monitoring has received surprisingly little attention. In this article, we share our experiences and review existing literature on this subject.
Topics: Adult; Child; Diffusion Magnetic Resonance Imaging; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Neoplasm Staging; Neoplasms; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Whole Body Imaging
PubMed: 33929564
DOI: 10.1007/s00247-021-05076-x -
The Quarterly Journal of Nuclear... Mar 2021During the past 10 years, performing real-time molecular imaging with positron emission tomography (PET) in combination with computed tomography (CT) during... (Review)
Review
During the past 10 years, performing real-time molecular imaging with positron emission tomography (PET) in combination with computed tomography (CT) during interventional procedures has undergone rapid development. Keeping in mind the interest of the nuclear medicine readers, an update is provided of the current workflows using real-time PET/CT in percutaneous biopsies and tumor ablations. The clinical utility of PET/CT guided biopsies in cancer patients with lung, liver, lymphoma, and bone tumors are reviewed. Several technological developments, including the introduction of new PET tracers and robotic arms as well as opportunities provided through acquiring radioactive biopsy specimens are briefly reviewed.
Topics: Bone Neoplasms; Dose-Response Relationship, Radiation; Fluorodeoxyglucose F18; Humans; Liver; Lung; Lymphoma; Nuclear Medicine; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed
PubMed: 33494585
DOI: 10.23736/S1824-4785.21.03291-X -
Scientific Reports Jun 2023Glioblastoma, a malignant tumor, has no curative treatment. Recently, mitochondria have been considered a potential target for treating glioblastoma. Previously, we...
Glioblastoma, a malignant tumor, has no curative treatment. Recently, mitochondria have been considered a potential target for treating glioblastoma. Previously, we reported that agents initiating mitochondrial dysfunction were effective under glucose-starved conditions. Therefore, this study aimed to develop a mitochondria-targeted treatment to achieve normal glucose conditions. This study used U87MG (U87), U373, and patient-derived stem-like cells as well as chloramphenicol (CAP) and 2-deoxy-D-glucose (2-DG). We investigated whether CAP and 2-DG inhibited the growth of cells under normal and high glucose concentrations. In U87 cells, 2-DG and long-term CAP administration were more effective under normal glucose than high-glucose conditions. In addition, combined CAP and 2-DG treatment was significantly effective under normal glucose concentration in both normal oxygen and hypoxic conditions; this was validated in U373 and patient-derived stem-like cells. 2-DG and CAP acted by influencing iron dynamics; however, deferoxamine inhibited the efficacy of these agents. Thus, ferroptosis could be the underlying mechanism through which 2-DG and CAP act. In conclusion, combined treatment of CAP and 2-DG drastically inhibits cell growth of glioblastoma cell lines even under normal glucose conditions; therefore, this treatment could be effective for glioblastoma patients.
Topics: Humans; Glioblastoma; Ferroptosis; Chloramphenicol; Glucose; Deoxyglucose
PubMed: 37380755
DOI: 10.1038/s41598-023-37483-5 -
The Journal of Thoracic and... Mar 2020
Topics: Disasters; Fluorodeoxyglucose F18; Humans; Lung Diseases, Interstitial; Lung Neoplasms
PubMed: 31619331
DOI: 10.1016/j.jtcvs.2019.08.124 -
Seminars in Nuclear Medicine Mar 2022Nuclear medicine procedures are generally avoided during pregnancy out of concern for the radiation dose to the fetus. However, for clinical reasons,... (Review)
Review
Nuclear medicine procedures are generally avoided during pregnancy out of concern for the radiation dose to the fetus. However, for clinical reasons, radiopharmaceuticals must occasionally be administered to pregnant women. The procedures most likely to be performed voluntarily during pregnancy are lung scans to diagnose pulmonary embolism and F-fluoro-2-deoxyglucose (F-FDG) scans for the staging of cancers. This article focuses on the challenges of fetal dose calculation after administering radiopharmaceuticals to pregnant women. In particular, estimation of the fetal dose is hampered by the lack of fetal biokinetic data of good quality and is subject to the variability associated with methodological choices in dose calculations, such as the use of various anthropomorphic phantoms and modeling of the maternal bladder. Despite these sources of uncertainty, the fetal dose can be reasonably calculated within a range that is able to inform clinical decisions. Current dose estimates suggest that clinically justified nuclear medicine procedures should be performed even during pregnancy because the clinical benefits for the mother and the fetus outweigh the small and purely hypothetical radiation risk to the fetus. In addition, the fetal radiation dose should be minimized without compromising image quality, such as by encouraging bladder voiding and by using positron emission tomography (PET)/magnetic resonance imaging (MRI) devices or high-sensitivity PET scanners that generate images of good quality with a lower injected activity.
Topics: Female; Fetus; Fluorodeoxyglucose F18; Humans; Positron-Emission Tomography; Pregnancy; Radiation Dosage; Radiopharmaceuticals
PubMed: 35067360
DOI: 10.1053/j.semnuclmed.2021.12.007 -
Journal of the American College of... Sep 2019
Topics: Fluorodeoxyglucose F18; Humans; Plaque, Atherosclerotic; Positron-Emission Tomography
PubMed: 31466621
DOI: 10.1016/j.jacc.2019.07.009