PET of Brain Prion Protein Amyloid in Gerstmann–Sträussler–Scheinker Disease

In vivo amyloid PET imaging was carried out on six symptomatic and asymptomatic carriers of PRNP mutations associated with the Gerstmann-Sträussler-Scheinker (GSS) disease, a rare familial neurodegenerative brain disorder demonstrating prion amyloid neuropathology, using 2- (1-6- (2-[F-18fluoroethyl) (methyl) amino]-2-naphthylethylidene) malononitrile (F-18FDDNP). 2-Deoxy-2-F-18fluoro-d-glucose PET (F-18FDG) and magnetic resonance imaging (MRI) scans were also performed in each subject. Increased F-18FDDNP binding was detectable in cerebellum, neocortex and subcortical areas of all symptomatic gene carriers in close association with the experienced clinical symptoms. Parallel glucose metabolism (F-18FDG) reduction was observed in neocortex, basal ganglia and/or thalamus, which supports the close relationship between F-18FDDNP binding and neuronal dysfunction. Two asymptomatic gene carriers displayed no cortical F-18FDDNP binding, yet progressive F-18FDDNP retention in caudate nucleus and thalamus was seen at 1- and 2-year follow-up in the older asymptomatic subject. In vitro FDDNP labeling experiments on brain tissue specimens from deceased GSS subjects not participating in the in vivo studies indicated that in vivo accumulation of F-18FDDNP in subcortical structures, neocortices and cerebellum closely related to the distribution of prion protein pathology. These results demonstrate the feasibility of detecting prion protein accumulation in living patients with F-18FDDNP PET, and suggest an opportunity for its application to follow disease progression and monitor therapeutic interventions.