SYNTHESIS AND ORGAN DISTRIBUTION OF [F-18]FLUORO-ORG-6141 IN THE RAT - A POTENTIAL GLUCOCORTICOID RECEPTOR-LIGAND FOR POSITRON EMISSION TOMOGRAPHY

For the synthesis of [F-18]Fluoro-Org 6141 via a nucleophilic substitu tion reaction with F-18(-), the tosyl group was chosen as the leaving group because of its stability and excellent leaving group ability. Th e biodistribution of the high affinity and moderate lipophilicity (log P = 2.66, calculated value) ligand [F-18]Fluoro-Org 6141 (specific ac tivity 8.2 to 37 TBq/mmol, yield 10% at EOB) was examined in sham adre nalectomized (sADX) and adrenalectomized (ADX) male Wistar rats. Two d ays after ADX or sADX, the animals were anesthetized acid 0.37 to 1.85 MBq of [F-18]Fluoro-Org 6141 was administered intravenously. Kinetics of F-18 activity uptake were monitored for 3 h using a stationary dou ble-headed positron emission tomography (PET) camera, and the biodistr ibution was assessed by ex vivo determination of radioactivity in seve ral tissues and different brain areas. One hour after injection of the radioligand, the bladder, kidney, liver, trachea, and bone of sADX an imals contained more concentration on a wet weight basis than blood. T hree hours post injection, radioactivity was retained in bladder, trac hea, and bone. The accumulation of radioactivity in brain corresponded to the concentration of activity in the blood within the first hours after injection. ADX animals showed a higher uptake of F-18 activity i n spleen, testes, and brain areas (hippocampus and brainstem) but a lo wer uptake in bone than sADX rats. PET scans suggested that F-18 activ ity uptake in the brain had not yet reached a maximum at this interval . Although [F-18]Fluoro-Org 6141 is not useful for PET studies of gluc ocorticoid receptors (GRs), the results obtained with this compound in dicate a synthetic strategy suitable for the synthesis of high-affinit y radioligands for GRs.