2-fluoro-2-deoxyglucose-6-phosphate and Disease-Models--Animal

Topics: Animals; Antineoplastic Agents; Disease Models, Animal; Drug Resistance, Neoplasm; Female; Glucose-6-Phosphate; Glycolysis; Mice; Mice, Nude; Neovascularization, Pathologic; Paraganglioma; Positron-Emission Tomography; Sunitinib; Tomography, X-Ray Computed; Tumor Escape; Ultrasonography

Atherosclerosis is a self-sustaining inflammatory fibroproliferative disease that progresses in discrete stages and involves a number of cell types and effector molecules. Recently, [

Topics: Animals; Aorta; Cholesterol; Dietary Fats; Disease Models, Animal; Glucose-6-Phosphate; Macaca fascicularis; Male; Muscle, Smooth, Vascular; Plaque, Atherosclerotic; Positron-Emission Tomography; Rabbits

Cortical spreading depression (SD) is a self-propagating wave of depolarization that is thought to be an underling mechanism of migraine aura. Growing evidence demonstrates that cortical SD triggers neurogenic meningeal inflammation and contributes to migraine headaches via subsequent activation of trigeminal afferents. Although direct and indirect evidence shows that cortical SD activates the trigeminal ganglion (peripheral pathway) and the trigeminal nucleus caudalis (TNC, the first central site of the trigeminal nociceptive pathway), it is not yet known whether cortical SD activates the high-order trigeminal nociceptive pathway in the brain. To address this, we induced unilateral cortical SD in rats, and then examined brain activity using voxel-based statistical parametric mapping analysis of FDG-PET imaging. The results show that approximately 40h after the induction of unilateral cortical SD, regional brain activity significantly increased in several regions, including ipsilateral TNC, contralateral ventral posteromedial (VPM) and posterior thalamic nuclei (Po), the trigeminal barrel-field region of the primary somatosensory cortex (S1BF), and secondary somatosensory cortex (S2). These results suggest that cortical SD is a noxious stimulus that can activate the high-order trigeminal nociceptive pathway even after cortical SD has subsided, probably due to prolonged meningeal inflammation.

Topics: Animals; Cortical Spreading Depression; Disease Models, Animal; Glucose-6-Phosphate; Image Processing, Computer-Assisted; Laser-Doppler Flowmetry; Male; Migraine Disorders; Neural Pathways; Positron-Emission Tomography; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Trigeminal Caudal Nucleus; Trigeminal Nerve

To monitor a real-time follow-up of tumor response to photodynamic therapy (PDT) by dynamic 2-deoxy-2-[(18)F]fluoro-d-glucose ((18)FDG) and positron emission tomography (PET) using two photosensitizing drugs in vivo, and to assess their mechanisms of action.. Two types of photosensitizers with different action mechanisms were used in rats implanted with two tumors: AlPcS4 mainly affecting the tumor vascular system, and ZnPcS2 largely inducing direct cell kill. Twenty-four hours after administration of either photosensitizer, one tumor served as control while the other was treated with red light during 30min within the 2h PET imaging by infusion of (18)FDG. The usual two-tissue compartment kinetic model was modified to take into account the perturbation of the treatment during imaging.. The illumination of the tumors during PET imaging provoked a net decrease of (18)FDG uptake in tumors treated with AlPcS4 and a near total absence of (18)FDG uptake in tumors treated with ZnPcS2. After the end of illumination, the tumors regained (18)FDG uptake with a more pronounced uptake in the tumors treated with ZnPcS2. The rate constant values of the new (18)FDG kinetic model reflected the response of the tumors to the treatment in both photosensitizers.. Dynamic PET imaging can be used to quantitatively assess in vivo and in real-time the response of tumors to treatments. It is demonstrated that the 30min of treatment was not sufficient to reduce the activity of the tumors. The technique could be extended to directly monitor the effects of drugs in vivo.

Topics: Animals; Disease Models, Animal; Glucose-6-Phosphate; Indoles; Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Positron-Emission Tomography; Rats

Uterine sarcomas are rare and aggressive gynecologic tumors with a poor prognosis because of recurrence and metastasis. However, the mechanisms of uterine sarcoma metastasis are largely unknown. To investigate this mechanism, we developed a novel uterine sarcoma tissue-derived orthotopic and metastatic model in KSN nude mice using a green fluorescent protein stably expressed uterine sarcoma cell line, MES-SA. Histological analysis showed that all orthotopic primary tumors were undifferentiated sarcoma. Primary tumors were characterized by high (18)F-fluorodeoxyglucose uptake with a positive correlation to the number of pulmonary metastases. In addition, we generated uterine sarcoma cell sublines with high or low metastatic potentials by serial in vivo selection. Microarray analysis between orthotopic tumors with high and low metastatic potentials revealed differential expression of genes related to cell proliferation and migration (TNNT1, COL1A2, and ZIC1). Our model would be useful to compensate for the limited clinical cases of uterine sarcoma and to investigate the molecular mechanisms of metastatic uterine sarcoma.

Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Female; Glucose Transport Proteins, Facilitative; Glucose-6-Phosphate; Humans; Lung Neoplasms; Mice; Mice, Nude; Positron-Emission Tomography; Sarcoma; Transcription Factors; Troponin T; Tumor Cells, Cultured; Uterine Neoplasms

(18)F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging of atherosclerosis in the clinic is based on preferential accumulation of radioactive glucose analog in atherosclerotic plaques. FDG-PET is challenging in mouse models due to limited resolution and high cost. We aimed to quantify accumulation of nonradioactive glucose metabolite, FDG-6-phosphate, in the mouse atherosclerotic plaques as a simple alternative to PET imaging.. Nonradioactive FDG was injected 30 minutes before euthanasia. Arteries were dissected, and lipids were extracted. The arteries were re-extracted with 50% acetonitrile-50% methanol-0.1% formic acid. A daughter ion of FDG-6-phosphate was quantified using liquid chromatography and mass spectrometry (LC/MS/MS). Thus, both traditional (cholesterol) and novel (FDG-6-phosphate) markers were assayed in the same tissue. FDG-6-phosphate was accumulated in atherosclerotic lesions associated with carotid ligation of the Western diet fed ApoE knockout mice (5.9 times increase compare to unligated carotids, p<0.001). Treatment with the liver X receptor agonist T0901317 significantly (2.1 times, p<0.01) reduced FDG-6-phosphate accumulation 2 weeks after surgery. Anti-atherosclerotic effects were independently confirmed by reduction in lesion size, macrophage number, cholesterol ester accumulation, and macrophage proteolytic activity.. Mass spectrometry of FDG-6-phosphate in experimental atherosclerosis is consistent with plaque inflammation and provides potential translational link to the clinical studies utilizing FDG-PET imaging.

Topics: Animals; Apolipoproteins E; Arteries; Atherosclerosis; Carotid Arteries; Cell Line; Chemistry, Pharmaceutical; Cholesterol; Chromatography, Liquid; Diagnostic Imaging; Disease Models, Animal; Drug Design; Glucose; Glucose-6-Phosphate; Humans; Hydrocarbons, Fluorinated; Ions; Liver X Receptors; Mass Spectrometry; Mice; Mice, Inbred C57BL; Mice, Knockout; Orphan Nuclear Receptors; Plaque, Atherosclerotic; Positron-Emission Tomography; Sulfonamides; Time Factors

The biophysical mechanism(s) underlying diffusion-weighted MRI contrast following brain injury remains to be elucidated. Although it is generally accepted that water apparent diffusion coefficient (ADC) decreases after brain injury, it is unknown whether this is associated with a decrease in intracellular or extracellular water displacement, or both. To address this question, 2-[19F]luoro-2-deoxyglucose-6-phosphate (2FDG-6P) was employed as a compartment-specific marker in normal and globally ischemic rat brain. Through judicious choice of routes of administration, 2FDG-6P was confined to the intra- or extracellular space. There was no statistical difference between intra- and extracellular 2FDG-6P ADCs in normal or in globally ischemic brain (P > 0.16), suggesting that water ADCs in both compartments are similar. However, ischemia did result in a 40% ADC decrease in both compartments (P < 0.001). Assuming that 2FDG-6P reflects water motion, this study shows that water ADC decreases in both spaces after ischemia, with the reduction of intracellular water motion being the primary source of diffusion-weighted contrast.

Topics: Animals; Biomarkers; Brain; Brain Ischemia; Cells, Cultured; Diffusion; Disease Models, Animal; Extracellular Space; Fluorine; Glucose-6-Phosphate; Intracellular Fluid; Magnetic Resonance Spectroscopy; Male; Mice; Neuroglia; Neurons; Phantoms, Imaging; Rats; Rats, Sprague-Dawley; Reference Values; Sensitivity and Specificity