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:
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.
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:
Couples; Binding (Molecular Function); Molecular Interaction; Binding; Diagnosis; Disease; disease/disorder; Disorder; Pharmaceutical Preparations; drug/agent; Pharmaceutic Preparations; Medication; Drugs; small molecule; Enzyme-Linked Immunosorbent Assay; ELISA; Affinity; Clinical Drug Development; Clinical Drug Testing/Development; Applications Grants; Grant Proposals; Resolution; in vivo; Ligand Binding; Rodent Model; Monitor; Molecular; Development; developmental; molecular imaging; Image; imaging; Pathway interactions; pathway; pre-clinical; preclinical; Noble Gases; gas element; Rare Gases; Inert Gases; Group 18 Elements; Injury; base; density; Organ; improved; Hand; Human; Modern Man; Man (Taxonomy); Peripheral; Diffuse; Variant; Variation; Biological; Medical; Benzodiazepine Receptor; Diazepam Receptors; Link; In Vitro; Inflammation; Chemicals; Ligands; Discipline; Alzheimer's Disease; senile dementia of the Alzheimer type; primary degenerative dementia; dementia of the Alzheimer type; Primary Senile Degenerative Dementia; Alzheimers disease; Alzheimers Dementia; Alzheimer's; Alzheimer syndrome; Alzheimer sclerosis; Alzheimer disease; Alzheimer Type Dementia; Alzheimer; Magnetic Resonance Imaging; Zeugmatography; Nuclear Magnetic Resonance Imaging; NMR Tomography; NMR Imaging; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Magnetic Resonance Imaging Scan; MRI; MR Tomography; MR Imaging; Medicine; Methods; Molecular Probes; Molecular Structure; Macromolecular Structure; Multiple Sclerosis; insular sclerosis; MS (Multiple Sclerosis); Disseminated Sclerosis; Brain Injuries; brain lesion (from injury); brain damage; Acquired brain injury; Nerve Growth Factors; Neurotrophic Proteins; Neuronotrophic Factors; Biological Process; Biological Function; Organism; living system; Parkinson Disease; Primary Parkinsonism; Parkinsons disease; Parkinson's disease; Parkinson's; Parkinson; Paralysis Agitans; Lewy Body Parkinson Disease; Idiopathic Parkinson Disease; Animals; Pathology; Patients; Antibodies; Monoclonal Antibodies; Clinical Treatment Moab; Positron-Emission Tomography; Rad.-PET; Positron Emission Tomography Scan; Positron Emission Tomography Medical Imaging; PETT; PETSCAN; PET imaging; PET Scan; PET; Ionizing radiation; Radiation-Ionizing Total; Ionizing Electromagnetic Radiation; Radio Waves; radiowave radiation; Hertzian Waves; Radioisotopes; Radionuclides; Radioactive Isotopes; Diagnostic; Research Personnel; Researchers; Investigators; Signal Transduction; biological signal transduction; Signaling; Signal Transduction Systems; Intracellular Communication and Signaling; Cell Signaling; Cell Communication and Signaling; Life; Specificity; Technology; Testing; Time; Tissues; Body Tissues; Emission-Computed Tomography; radionuclide emission tomography; Radionuclide CAT Scan; Computerized Emission Tomography; Computed Tomographic Scintigraphy; Atherosclerosis; atherosclerotic vascular disease; atheromatosis; Atherosclerotic Cardiovascular Disease; Atheroscleroses; Ultrasonography; ultrasound scanning; ultrasound imaging; ultrasound; sound measurement; sonography; sonogram; diagnostic ultrasound; Ultrasound Test; Ultrasound Medical Imaging; Ultrasound Diagnosis; Ultrasonogram; Ultrasonic Imaging; Medical Ultrasound; Echotomography; Echography; Vertebrates; vertebrata; Vertebrate Animals; Water; Hydrogen Oxide; Roentgen Rays; Xrays; X-Rays Radiation; X-Rays; X-Radiation; Radiation, X-Rays, Gamma-Rays; Xenon; Xe element; Complex; Protocols documentation; Protocol; Techniques; brain tissue; experience; physical property; receptor binding; cellular targeting; Biosensor; sensor (biological); Brain; Encephalon; Brain Nervous System; Brain Pathology; Structure; peer; new technology; novel technologies; Cell Membrane Permeability; membrane permeability; Cultured Cells; Imaging Techniques; Imaging Technics; Imaging Procedures; Measures; Photons; Property; LOINC Axis 2 Property; cellular engineering; cell engineering; protein distribution; Traumatic Brain Injury; traumatic brain damage; Traumatic encephalopathy; Brain Trauma; Magnetic Resonance; imaging probe; Imaging technology; prototype; public health relevance; biomarker
