Synthesis and radiopharmacological characterization of [¹¹C]AL-438 as a nonsteroidal ligand for imaging brain glucocorticoid receptors

The radiosynthesis and the radiopharmacological characterization of [¹¹C]AL-438 as a nonsteroidal ligand for the glucocorticoid receptor (GR) is described. Radiolabelling of the corresponding desmethyl precursor 10 with [¹¹C]MeI gave [¹¹C]AL-438 in decay-corrected radiochemical yields of 30±4% (based upon [¹¹C]CO₂) within 35 min at a specific radioactivity of 10-15 GBq/µmol at the end-of-synthesis. The radiopharmacological evaluation of [¹¹C]AL-438 involved biodistribution and small animal PET imaging in rats, and autoradiography studies using rat brain sections.
Biodistribution studies were performed in male Wistar rats and demonstrated high radio-activity uptake in pituitary and brain. However, the inability of high dose corticosterone to block binding would suggest that the radioactivity accumulation in the brain was not receptor-mediated.