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-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]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 [18F]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 K18F/Kryptofix 2.2.2. yielded chemically (>99%) and radiochemically (>99%) pure [18F]FDDNP in high radiochemical yields (40–60%; n> 120), with specific activities ranging from 4 to 8 Ci/μmol 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 [18F]fluoride) of [18F]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.

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