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Journal of Nuclear Medicine : Official... Aug 2021Imaging plays a critical role in the management of pheochromocytomas and paragangliomas and often guides treatment. The discovery of susceptibility genes associated with...
Imaging plays a critical role in the management of pheochromocytomas and paragangliomas and often guides treatment. The discovery of susceptibility genes associated with these tumors has led to better understanding of clinical and imaging phenotypes. Functional imaging is of prime importance because of its sensitivity and specificity in subtypes of pheochromocytoma and paraganglioma. Several radiopharmaceuticals have been developed to target specific receptors and metabolic processes seen in pheochromocytomas and paragangliomas, including I/I-metaiodobenzylguanidine, 6-F-fluoro-l-3,4-dihydroxyphenylalanine, F-FDG, and Ga-DOTA-somatostatin analogs. Two of these have consequently been adapted for therapy. This educational review focuses on the current imaging approaches used in pheochromocytomas and paragangliomas, which vary among clinical and genotypic presentations.
Topics: Fluorodeoxyglucose F18; Humans; Paraganglioma; Pheochromocytoma; Positron Emission Tomography Computed Tomography
PubMed: 34330739
DOI: 10.2967/jnumed.120.259689 -
International Journal of Molecular... Dec 2019The ability of 2-deoxy-d-glucose (2-DG) to interfere with d-glucose metabolism demonstrates that nutrient and energy deprivation is an efficient tool to suppress cancer... (Review)
Review
The ability of 2-deoxy-d-glucose (2-DG) to interfere with d-glucose metabolism demonstrates that nutrient and energy deprivation is an efficient tool to suppress cancer cell growth and survival. Acting as a d-glucose mimic, 2-DG inhibits glycolysis due to formation and intracellular accumulation of 2-deoxy-d-glucose-6-phosphate (2-DG6P), inhibiting the function of hexokinase and glucose-6-phosphate isomerase, and inducing cell death. In addition to glycolysis inhibition, other molecular processes are also affected by 2-DG. Attempts to improve 2-DG's drug-like properties, its role as a potential adjuvant for other chemotherapeutics, and novel 2-DG analogs as promising new anticancer agents are discussed in this review.
Topics: Cell Death; Combined Modality Therapy; Deoxyglucose; Glioblastoma; Glucose; Glucose-6-Phosphate; Glucose-6-Phosphate Isomerase; Glycolysis; Hexokinase; Humans
PubMed: 31905745
DOI: 10.3390/ijms21010234 -
Journal of Neuroinflammation Jun 2021Microglial activation-mediated neuroinflammation plays an important role in the progression of neurodegenerative diseases. Inflammatory activation of microglial cells is...
BACKGROUND
Microglial activation-mediated neuroinflammation plays an important role in the progression of neurodegenerative diseases. Inflammatory activation of microglial cells is often accompanied by a metabolic switch from oxidative phosphorylation to aerobic glycolysis. However, the roles and molecular mechanisms of glycolysis in microglial activation and neuroinflammation are not yet fully understood.
METHODS
The anti-inflammatory effects and its underlying mechanisms of glycolytic inhibition in vitro were examined in lipopolysaccharide (LPS) activated BV-2 microglial cells or primary microglial cells by enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, immunoprecipitation, flow cytometry, and nuclear factor kappa B (NF-κB) luciferase reporter assays. The anti-inflammatory and neuroprotective effects of glycolytic inhibitor, 2-deoxoy-D-glucose (2-DG) in vivo were measured in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-or LPS-induced Parkinson's disease (PD) models by immunofluorescence staining, behavior tests, and Western blot analysis.
RESULTS
We found that LPS rapidly increased glycolysis in microglial cells, and glycolysis inhibitors (2-DG and 3-bromopyruvic acid (3-BPA)), siRNA glucose transporter type 1 (Glut-1), and siRNA hexokinase (HK) 2 abolished LPS-induced microglial cell activation. Mechanistic studies demonstrated that glycolysis inhibitors significantly inhibited LPS-induced phosphorylation of mechanistic target of rapamycin (mTOR), an inhibitor of nuclear factor-kappa B kinase subunit beta (IKKβ), and NF-kappa-B inhibitor alpha (IκB-α), degradation of IκBα, nuclear translocation of p65 subunit of NF-κB, and NF-κB transcriptional activity. In addition, 2-DG significantly inhibited LPS-induced acetylation of p65/RelA on lysine 310, which is mediated by NAD-dependent protein deacetylase sirtuin-1 (SIRT1) and is critical for NF-κB activation. A coculture study revealed that 2-DG reduced the cytotoxicity of activated microglia toward MES23.5 dopaminergic neuron cells with no direct protective effect. In an LPS-induced PD model, 2-DG significantly ameliorated neuroinflammation and subsequent tyrosine hydroxylase (TH)-positive cell loss. Furthermore, 2-DG also reduced dopaminergic cell death and microglial activation in the MPTP-induced PD model.
CONCLUSIONS
Collectively, our results suggest that glycolysis is actively involved in microglial activation. Inhibition of glycolysis can ameliorate microglial activation-related neuroinflammatory diseases.
Topics: Animals; Brain; Coculture Techniques; Cytokines; Deoxyglucose; Dopaminergic Neurons; Glycolysis; HEK293 Cells; Humans; Lipopolysaccharides; Mice; Microglia; NF-kappa B; Neuroinflammatory Diseases; Neuroprotective Agents; Rats; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 34107997
DOI: 10.1186/s12974-021-02187-y -
International Journal of Molecular... Mar 2021Metabolism reprogramming influences the severity of organ dysfunction, progression to fibrosis, and development of disease in acute kidney injury (AKI). Previously we...
Metabolism reprogramming influences the severity of organ dysfunction, progression to fibrosis, and development of disease in acute kidney injury (AKI). Previously we showed that inhibition of aerobic glycolysis improved survival rates and protected septic mice from kidney injury. However, the underlying mechanisms remain unclear. In the present study, it was revealed that sepsis or lipopolysaccharide (LPS) enhanced aerobic glycolysis as evidenced by increased lactate production and upregulated mRNA expression of glycolysis‑related genes in kidney tissues and human renal tubular epithelial (HK‑2) cells. The aerobic glycolysis inhibitor 2‑deoxy‑D‑glucose (2‑DG) downregulated glycolysis, and improved kidney injury induced by sepsis. 2‑DG treatments increased the expression of sirtuin 3 (SIRT3) and phosphorylation‑AMP‑activated protein kinase (p‑AMPK), following promoted autophagy and attenuated apoptosis of tubular epithelial cells in septic mice and in LPS‑treated HK‑2 cells. However, the glycolysis metabolite lactate downregulated SIRT3 and p‑AMPK expression, inhibited autophagy and enhanced apoptosis in LPS‑treated HK‑2 cells. Furthermore, pharmacological blockade of autophagy with 3‑methyladenine (3‑MA) partially abolished the protective effect of 2‑DG in sepsis‑induced AKI. These findings indicated that inhibition of aerobic glycolysis protected against sepsis‑induced AKI by promoting autophagy via the lactate/SIRT3/AMPK pathway.
Topics: AMP-Activated Protein Kinases; Acute Kidney Injury; Animals; Autophagy; Deoxyglucose; Glycolysis; Lactic Acid; Male; Mice; Mice, Inbred BALB C; Sepsis; Sirtuin 3
PubMed: 33448325
DOI: 10.3892/ijmm.2021.4852 -
International Heart Journal 2023
Topics: Humans; Fluorodeoxyglucose F18; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 37005309
DOI: 10.1536/ihj.23-053 -
Ugeskrift For Laeger Feb 2023
Topics: Humans; Polymyalgia Rheumatica; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Giant Cell Arteritis; Positron-Emission Tomography
PubMed: 36762378
DOI: No ID Found -
Journal of Nuclear Medicine Technology Jun 2021
Review
Topics: Fluorine Radioisotopes; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Sodium Fluoride
PubMed: 34083453
DOI: 10.2967/jnmt.121.262379 -
Molecules (Basel, Switzerland) Apr 2021Theranostics is a precision medicine which integrates diagnostic nuclear medicine and radionuclide therapy for various cancers throughout body using suitable tracers and... (Review)
Review
Theranostics is a precision medicine which integrates diagnostic nuclear medicine and radionuclide therapy for various cancers throughout body using suitable tracers and treatment that target specific biological pathways or receptors. This review covers traditional theranostics for thyroid cancer and pheochromocytoma with radioiodine compounds. In addition, recent theranostics of radioimmunotherapy for non-Hodgkin lymphoma, and treatment of bone metastasis using bone seeking radiopharmaceuticals are described. Furthermore, new radiopharmaceuticals for prostatic cancer and pancreatic cancer have been added. Of particular, F-18 Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography (PET) is often used for treatment monitoring and estimating patient outcome. A recent clinical study highlighted the ability of alpha-radiotherapy with high linear energy transfer (LET) to overcome treatment resistance to beta--particle therapy. Theranostics will become an ever-increasing part of clinical nuclear medicine.
Topics: Animals; Fluorodeoxyglucose F18; Humans; Neoplasms; Positron Emission Tomography Computed Tomography; Radioisotopes; Therapeutics
PubMed: 33924345
DOI: 10.3390/molecules26082232 -
Jornal Brasileiro de Pneumologia :... Sep 2022
Topics: Fluorodeoxyglucose F18; Humans; Lung; Lung Diseases, Interstitial; Positron Emission Tomography Computed Tomography
PubMed: 36074412
DOI: 10.36416/1806-3756/e20220293 -
Seminars in Radiation Oncology Jul 2023PET imaging with 2'-deoxy-2'-[18F]fluoro-D-glucose ([18F]FDG) has become one of the pillars in the management of malignant diseases. It has proven value in diagnostic... (Review)
Review
PET imaging with 2'-deoxy-2'-[18F]fluoro-D-glucose ([18F]FDG) has become one of the pillars in the management of malignant diseases. It has proven value in diagnostic workup, treatment policy, follow-up, and as prognosticator for outcome. [18F]FDG is widely available and standards have been developed for PET acquisition protocols and quantitative analyses. More recently, [18F]FDG-PET is also starting to be appreciated as a decision aid for treatment personalization. This review focuses on the potential of [18F]FDG-PET for individualized radiotherapy dose prescription. This includes dose painting, gradient dose prescription, and [18F]FDG-PET guided response-adapted dose prescription. The current status, progress, and future expectations of these developments for various tumor types are discussed.
Topics: Humans; Fluorodeoxyglucose F18; Positron-Emission Tomography; Neoplasms; Glucose; Radiopharmaceuticals
PubMed: 37331783
DOI: 10.1016/j.semradonc.2023.03.006