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.
The purpose of this new grant application is to develop a fluorine-18 radioligand to measure glucorticoid receptor (GR) expression. This project will consist of the radiofluorination of the lead molecule, a preclinical assessment of its pharmacology in rodents, and a first in human study in healthy volunteers. The data from this project will confer upon the community a new translational imaging tool to study the role of GR expression changes in major public health challenges like depression for which tissue access is not possible in living subjects.
|Truillet, Charles; Parker, Matthew F L; Huynh, Loc T et al. (2018) Measuring glucocorticoid receptor expression in vivo with PET. Oncotarget 9:20399-20408|