开发和翻译一种新型放射性配体，用于测量大脑中糖皮质激素受体表达的病理变化-猫眼课题宝

开发和翻译一种新型放射性配体，用于测量大脑中糖皮质激素受体表达的病理变化

批准号：

9427881

负责人：

Michael John Evans

金额：

$69.08万

依托单位：

UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

依托单位国家：

美国

项目类别：

财政年份：

2017

资助国家：

美国

项目状态：

已结题

起止时间：

2017-12-01 至 2020-11-30

来源：

https://reporter.nih.gov/project-details/9427881

关键词：

Address Adopted Adrenal Cortex Hormones Adrenalectomy Affinity Androgen Receptor Animal Model Animals Antidepressive Agents Antineoplastic Agents Applications Grants Back Basic Science Binding Biodistribution Biological Brain Breast Carbon Chemicals Chemistry Clinical Clinical Research Communities Data Development Drug Targeting Endocrinology Estrogen Receptors Family Female Fluorine Generations Glucocorticoid Receptor Goals Grant Hippocampus (Brain)Hormones Human Image Imaging Device In Vitro Injections Investigational Therapies Lead Libraries Ligands Major Depressive Disorder Malignant Neoplasms Measures Mental Depression Mood Disorders Mus Neurosciences Normal tissue morphology Nuclear Hormone Receptors Ovarian Pathologic Permeability Pharmaceutical Preparations Pharmacology Phenols Phenotype Positron-Emission Tomography Preparation Prostate Public Health Radiochemistry Rattus Receptor Signaling Reporting Research Project Grants Rodent Role Scanning Serum Proteins Signal Transduction Structure Systems Analysis Therapeutic Tissues Toxic effect Toxicology Translating Translations animal data base clinically relevant dosimetry drug development first-in-human healthy volunteer human study in vivo innovation male man nanomolar neuroimaging novel novel therapeutics pharmacokinetic characteristic pre-clinical radioligand radiotracer receptor receptor expression restoration serial imaging targeted treatment uptake

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Project Abstract The goal of this project is to develop a brain permeable radioligand targeting the glucocorticoid receptor (GR). A non-steroidal ligand with sub-nanomolar affinity for GR will be radiofluorinated in specific aim 1, and its pharmacology will be assessed in vitro. Specific binding for GR will be determined in vivo in mice during specific aim 2. Rat dosimetry estimates and toxicity will also be calculated for an eIND application. In specific aim 3, a first in man study will be conducted to determine human dosimetry. The data from this project will confer upon the community a new translational imaging tool to study the role of GR expression changes in severe mood disorders like depression.

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