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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

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Abstract

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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Acknowledgments

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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Authors and Affiliations

  1. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California–Los Angeles, 10833 Le Conte Avenue CHS B2-086, Los Angeles, CA, 90095, USA

    Jie Liu PhD, Vladimir Kepe PhD, Nagichettiar Satyamurthy PhD & Jorge R. Barrio PhD

  2. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, SI-1000, Slovenia

    Alenka Žabjek PhD & Andrej Petrič PhD

  3. Siemens Biomarker Solutions, 6140 Bristol Parkway, Culver, CA, 90230, USA

    Henry C. Padgett PhD

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  1. Jie Liu PhD
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  2. Vladimir Kepe PhD
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  3. Alenka Žabjek PhD
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  4. Andrej Petrič PhD
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  7. Jorge R. Barrio PhD
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Correspondence to Jorge R. Barrio PhD.

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Liu, J., Kepe, V., Žabjek, A. et al. 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. Mol Imaging Biol 9, 6–16 (2007). https://doi.org/10.1007/s11307-006-0061-4

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  • DOI: https://doi.org/10.1007/s11307-006-0061-4

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