Development and translation of a novel radioligand to measure pathological changes in glucocorticoid receptor expression in the brain

项目摘要 本课题的目的是研制一种靶向糖皮质激素受体（GR）的脑渗透性放射性配体。 在具体目标1中，对GR具有亚纳摩尔亲和力的非甾体配体将被放射性氟化，并且其 将在体外评估药理学。将在小鼠体内测定GR的特异性结合， 具体目标2.还将计算eIND申请的大鼠剂量测定估计值和毒性。在特定 第三，将进行首次人体研究，以确定人体剂量。该项目的数据将 赋予社区一个新的翻译成像工具，研究GR表达变化的作用， 严重的情绪障碍比如抑郁症

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.