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The Journal of Neuroscience, September 3, 2003, 23(22):8029-8033

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Molecular-Imaging Probe 2-(1-{6-[(2-Fluoroethyl)(Methyl) Amino]-2-Naphthyl}Ethylidene) Malononitrile Labels Prion Plaques In Vitro

Mara Bresjanac,^1,2 Lojze M. Smid,^1,2 Tomaz D. Vovko,^1,2 Andrej Petri,³ Jorge R. Barrio,⁴ and Mara Popovic²

¹Laboratory for Neuronal Plasticity and Regeneration, Institute of Pathophysiology, ²Prion Laboratory, Institute of Pathology, School of Medicine, and ³Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 Ljubljana, Slovenia, and ⁴Division of Nuclear Medicine, Department of Molecular and Medical Pharmacology, Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles, School of Medicine, Los Angeles, California 90095

The study aimed to evaluate the fluorescent molecular-imaging probe 2-(1-{6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) for its ability to selectively and reproducibly label prion plaques in fixed, paraffin-embedded cerebellar sections from patients of confirmed Gerstmann-Sträussler-Scheinker disease, sporadic Creutzfeldt-Jacob disease (CJD) with kuru plaques, and variant CJD (vCJD). FDDNP is a highly hydrophobic, viscosity-sensitive, solvent-sensitive, fluorescent substance, whose radiofluorinated analog [¹⁸F]FDDNP has recently been successfully used to label senile plaques and neurofibrillary tangles in the living brain of Alzheimer's disease patients with positron emission tomography. Our results show that FDDNP reliably identifies all prion plaques, including small cluster-plaques in vCJD. This finding may open new in vivo diagnostic possibilities for vCJD.

Key words: fluorescent labeling; human; neuroimaging; TSE; variant Creutzfeldt-Jacob disease; amyloid

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Received April 8, 2003; revised May 27, 2003; accepted July 14, 2003.

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