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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH115043-01
Application #
9427881
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Michelotti, Enrique
Project Start
2017-12-01
Project End
2020-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118