Dysregulation of glucocorticoid receptor (GR) signaling has been implicated in Cushing’s syndrome, Addison’s disease, mood disorders, glomerular diseases and cancers (e.g. prostate cancer), but non-invasive biomarkers to better understand GR biology are needed.
UCSF researchers have developed a small molecule radioligand with ~100-fold more affinity for GR vs. other nuclear hormone receptors in the same family. YJH08 has sub-nM affinity for GR and binds GR on all normal tissues, including the brain. Use of this radioligand/theranostic can help identify patients most likely to respond to GR antagonists and could help develop tissue-specific GR-targeting drugs.
11C-YJH08 is currently in clinical trials at UCSF to evaluate GR expression in normal tissues and treatment resistant cancer cells (NCT04927663).
· Non-invasive biomarker for detecting GR expression in vivo
· Quantitative assessment in real time and multiple tissues simultaneously
· Selective for GR
· Clinical trials – to identify prostate cancer patients whose cancer is driven by GR activity
· Clinical trials – for development of GR antagonists as therapeutics
· Radiotracer to measure glucocorticoid receptor expression levels in vivo with PET
Huang, Y., et al. (2020). A Novel Radioligand Reveals Tissue Specific Pharmacological Modulation of Glucocorticoid Receptor Expression with Positron Emission Tomography. ACS chemical biology, 15(6), 1381–1391. https://doi.org/10.1021/acschembio.9b01043
Pending in the United States only
Michael Evans, PhD