This proposal describes the development of hyperpolarized-129Xenon (HP-Xe)-based probes for magnetic resonance imaging (MRI) of two biomarkers of inflammation and brain injury, the peripheral benzodiazepine receptor (PBR) and the neurotrophic protein, S100B. Molecular imaging (MI) is an emerging discipline that tries to non-invasively visualize specific biomolecules in living organisms and has many medical applications with immense commercial potential. For example, MI-based biomarkers will allow for better treatment of disease through earlier and more precise diagnosis. In addition, they will help to shorten pre-clinical and clinical drug-development protocols by more sensitively and quantitatively measuring the biological actions of new medications. The sensitivity of positron emission tomography (PET) and single photon emission computed tomography (SPECT) have led to the widespread use of these technologies for imaging specific bio-molecules in vivo. However, PET and SPECT have very poor spatial resolution (mm-cm) and use probes containing short-lived radioactive isotopes which emit tissue damaging ionizing radiation. MRI, on the other hand, utilizes relatively harmless radio-waves to image living organisms at close to cellular resolution (25-100
Public Health Relevance Statement: We are proposing to synthesize probe molecules that can be used in conjunction with magnetic resonance imaging (MRI) to non-invasively take very high resolution pictures of the distribution of proteins called peripheral benzodiazepine receptors (PBR) and S100B in the tissues and brains of human patients. It has been previously demonstrated that examining the distribution of PBR and S100B in this manner will help us to better diagnose, monitor progression of and treat serious diseases such as multiple sclerosis, atherosclerosis, Alzheimer's disease and Parkinson's disease.
Project Terms: Acquired brain injury; Affinity; Alzheimer; Alzheimer disease; Alzheimer sclerosis; Alzheimer syndrome; Alzheimer's; Alzheimer's Disease; Alzheimers Dementia; Alzheimers disease; Animals; Antibodies; Applications Grants; Atheroscleroses; Atherosclerosis; Atherosclerotic Cardiovascular Disease; Benzodiazepine Receptor; Binding; Binding (Molecular Function); Biological; Biological Function; Biological Process; Biosensor; Body Tissues; Brain; Brain Injuries; Brain Pathology; CAT Scan, Radionuclide; Cell Communication and Signaling; Cell Membrane Permeability; Cell Signaling; Chemicals; Clinical Drug Development; Complex; Computerized Emission Tomography; Couples; Cultured Cells; Dementia, Alzheimer Type; Dementia, Primary Senile Degenerative; Dementia, Senile; Development; Diagnosis; Diagnosis, Ultrasound; Diagnostic; Diffuse; Discipline; Disease; Disorder; Drug Development, Clinical; Drug Testing/Development, Clinical; Drugs; ELISA; Echography; Echotomography; Electromagnetic Radiation, Ionizing; Emission-Computed Tomography; Encephalon; Encephalons; Enzyme-Linked Immunosorbent Assay; Gases, Inert; Grant Proposals; Grants, Applications; Group 18 Elements; Hand; Hertzian Waves; Human; Human, General; Hydrogen Oxide; INFLM; Idiopathic Parkinson Disease; Image; Imaging Procedures; Imaging Techniques; Imaging technology; In Vitro; Inflammation; Injury; Intracellular Communication and Signaling; Investigators; Ionizing radiation; Lewy Body Parkinson Disease; Life; Ligand Binding; Ligands; Link; MR Imaging; MR Tomography; MRI; MS (Multiple Sclerosis); Macromolecular Structure; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Man (Taxonomy); Man, Modern; Measures; Medical; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Medical Imaging, Positron Emission Tomography; Medical Imaging, Ultrasound; Medication; Medicine; Methods; Methods and Techniques; Methods, Other; Moab, Clinical Treatment; Molecular; Molecular Interaction; Molecular Probes; Molecular Structure; Monitor; Monoclonal Antibodies; Multiple Sclerosis; NMR Imaging; NMR Tomography; Nerve Growth Factors; Nervous System, Brain; Neuronotrophic Factors; Neurotrophic Factors; Neurotrophic Proteins; Neurotrophins; Noble Gases; Nuclear Magnetic Resonance Imaging; Organ; Organism; PET; PET Scan; PET imaging; PETSCAN; PETT; Paralysis Agitans; Parkinson; Parkinson Disease; Parkinson's; Parkinson's disease; Parkinsons disease; Pathology; Pathway interactions; Patients; Peripheral; Pharmaceutic Preparations; Pharmaceutical Preparations; Photons; Positron Emission Tomography Scan; Positron-Emission Tomography; Primary Parkinsonism; Primary Senile Degenerative Dementia; Property; Property, LOINC Axis 2; Protocol; Protocols documentation; Proton Magnetic Resonance Spectroscopic Imaging; Rad.-PET; Radiation, X-Rays; Radiation, X-Rays, Gamma-Rays; Radiation-Ionizing Total; Radio Waves; Radioactive Isotopes; Radioisotopes; Radionuclides; Rare Gases; Receptors, Diazepam; Research Personnel; Researchers; Resolution; Rodent Model; Roentgen Rays; Science of Medicine; Scintigraphy, Computed Tomographic; Sclerosis, Disseminated; Signal Transduction; Signal Transduction Systems; Signaling; Specificity; Structure; Technics, Imaging; Techniques; Technology; Testing; Time; Tissues; Tomography, Emission-Computed; Trauma, Brain; Traumatic Brain Injury; Traumatic encephalopathy; Ultrasonic Imaging; Ultrasonogram; Ultrasonography; Ultrasound Test; Ultrasound, Medical; Variant; Variation; Vertebrate Animals; Vertebrates; Water; X-Radiation; X-Rays; Xe element; Xenon; Xrays; Zeugmatography; atheromatosis; atherosclerotic vascular disease; base; biological signal transduction; biomarker; brain damage; brain lesion (from injury); brain tissue; cell engineering; cellular engineering; cellular targeting; dementia of the Alzheimer type; density; diagnostic ultrasound; disease/disorder; drug/agent; experience; gas element; imaging; imaging probe; improved; in vivo; insular sclerosis; living system; membrane permeability; molecular imaging; new technology; pathway; peer; physical property; pre-clinical; preclinical; primary degenerative dementia; protein distribution; prototype; public health relevance; radionuclide emission tomography; radiowave radiation; receptor binding; senile dementia of the Alzheimer type; sensor (biological); small molecule; sonogram; sonography; sound measurement; traumatic brain damage; ultrasound; ultrasound imaging; ultrasound scanning; vertebrata
