Molecular Imaging and Biology

, Volume 9, Issue 1, pp 6–16 | Cite as

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

  • Jie Liu
  • Vladimir Kepe
  • Alenka Žabjek
  • Andrej Petrič
  • Henry C. Padgett
  • Nagichettiar Satyamurthy
  • Jorge R. BarrioEmail author
Research Article


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.

Key words

[F-18]FDDNP Beta-Amyloid fibrils Senile plaques (SPs) Neurofibrillary tangles (NFTs) Alzheimer’s disease (AD) PET 



The authors would like to thank the staff at the UCLA Biomedical Cyclotron for the help provided during the optimization of the [18F]FDDNP radiosynthesis. This work was supported by Department of Energy grant DE-FC03-02ER-ER63420.


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Copyright information

© Academy of Molecular Imaging 2006

Authors and Affiliations

  • Jie Liu
    • 1
  • Vladimir Kepe
    • 1
  • Alenka Žabjek
    • 2
  • Andrej Petrič
    • 2
  • Henry C. Padgett
    • 3
  • Nagichettiar Satyamurthy
    • 1
  • Jorge R. Barrio
    • 1
    Email author
  1. 1.Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLAUniversity of California–Los AngelesLos AngelesUSA
  2. 2.Faculty of Chemistry and Chemical TechnologyUniversity of LjubljanaLjubljanaSlovenia
  3. 3.Siemens Biomarker SolutionsCulverUSA

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