Fluorine-18 radiolabelling, biodistribution studies and preliminary pet evaluation of a new memantine derivative for imaging the NMDA receptor

A synthetic method has been established for preparing [F-18]1-amino-3-fluoromethyl-5-methyl-adamantane ([F-18]AFA). Biodistrubution of the radiotracer; in mice showed high brain uptake. The peak uptake (3.78 I.D/g organ) for the brain occurred at 30 min after injection. Accumulation of radioactivity in mouse brain was consistent with the known distribution of the NMDA receptors. The binding of [F-18]AFA to the phencyclidine (PCP) binding sites of the NMDA receptor complex and the sigma recognition sites in a Rhesus monkey was also examined using positron emission tomography (PET). The regional brain distribution of [F-18]AFA was changed by memantine and by (+)-MK-801, indicating competition for the same binding sites. Treatment with haloperidol caused a marked reduction of radioactivity uptake in all the brain regions examined. (-)-Butaclamol, which has pharmacological specificity for sigma sites, did not have any significant effects.