High-yield, automated radiosynthesis of 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP) ready for animal or human administration

The biomarker 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP) is used as a positron emission tomography (PET) imaging probe for Alzheimer's disease and other neurodegenerative diseases. A high-yield and fully automated synthesis of [F-18]FDDNP-along with the synthesis and characterization of non-radioactive FDDNP, a fluorescent probe derived from 2-(1,1-dicyanopropenyl-2)-6-dimethylaminonaphthalene (DDNP)-are reported. Radiofluorination of the tosyloxy precursor 2-{[6-(2,2-dicyano-1-methylvinyl)-2-naphthyl](methyl)amino}ethyl-4-methylbenzenesulfonate (DDNPTs) with (KF)-F-18/Kryptofix 2.2.2. yielded chemically (> 99%) and radiochemically (> 99%) pure [F-18]FDDNP in high radiochemical yields (40=60%; n > 120), with specific activities ranging from 4 to 8 Ci/mu mol at the end of synthesis (90 minutes). Both remote, semiautomated and automated synthesis procedures are described. Either approach provides a reliable method for production of large quantities (110-170 mCi from 500 mCi of [F-18]fluoride) of [F-18]FDDNP allowing for multiple PET experiments in the same day or for distribution of the tracer from a single cyclotron facility to PET imaging centers at various geographical distances.