Molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl) amino]-2-naphthyl]ethylidene) malononitrile labels prion

Mara Bresjanac1, Lojze M Smid, Tomaz D Vovko

  • 1Laboratory for Neuronal Plasticity and Regeneration, Institute of Pathophysiology, University of Ljubljana, SI-1000 Ljubljana, Slovenia. maja.bresjanac@mf.uni-lj.si

Insights

The fluorescent probe FDDNP effectively labels prion plaques in brain tissue from various human prion diseases. This technique shows promise for future in vivo diagnostics of variant Creutzfeldt-Jakob disease (vCJD).

Area of Science:

  • Neuroscience
  • Biochemistry
  • Medical Imaging

Background:

  • Prion diseases, including Gerstmann-Sträussler-Scheinker disease, Creutzfeldt-Jakob disease (CJD), and variant CJD (vCJD), are fatal neurodegenerative disorders.
  • Accurate diagnosis, especially for vCJD, remains challenging, necessitating improved diagnostic tools.

Purpose of the Study:

  • To assess the efficacy of the fluorescent molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene)malononitrile (FDDNP) in labeling prion plaques.
  • To determine if FDDNP can selectively and reproducibly identify prion plaques in fixed, paraffin-embedded human cerebellar tissue.

Main Methods:

  • Evaluation of FDDNP's fluorescent properties and its application to cerebellar sections from patients with confirmed prion diseases.
  • Comparison of FDDNP labeling with histopathological findings of prion plaques, including kuru plaques and small cluster-plaques in vCJD.

Main Results:

  • FDDNP reliably and reproducibly labeled all observed prion plaques across different forms of human prion disease.
  • The probe successfully identified even small cluster-plaques characteristic of vCJD.

Conclusions:

  • FDDNP is a sensitive and specific fluorescent probe for detecting prion plaques in fixed brain tissue.
  • These findings suggest that FDDNP, or its radiofluorinated analog [18F]FDDNP, holds potential for in vivo diagnosis of vCJD and other prion diseases.