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American Society for Experimental Neurotherapeutics Abstracts
August 2000

Imaging in Parkinson Disease—a Window to Neurodegeneration, a Tool to Assess Neuroprotection?

Arch Neurol. 2000;57(8):1237. doi:

Parkinson disease (PD) has been a model neurodegenerative disorder in which advances in neuroscience have informed, and in turn, have been informed by clinical neurology. In vivo imaging of the nigrostriatal dopamine system has provided a tool to bridge developments in basic neuroscience and clinical neurology and to identify markers for the chronic degenerative process in PD. During the last decade, neuroreceptor imaging has been used to monitor disease onset, severity, and progression, and the physiological conditions of the degenerative process. Several markers, most focused on the dopamine system, using positron emmission tomography (PET) and single photon emmission computed tomography (SPECT) technology have been used to asses PD. The 2 most mature imaging biomarkers are F-Dopa ([18F]-6-fluoro-L-Dopa) PET, which measures dopamine function, and [123I] β-CIT SPECT, which tags the dopamine transporter. In numerous studies, these ligands have demonstrated dopamine striatal deficits that identify symptomatic and presymptomatic subjects and that correlate with severity of PD. More recently, longitudinal imaging studies have shown that the dopamine loss in PD occurs at a rate of approximately 10%/y and have suggested that the preclinical phase of PD was 5 to 10 years. Ongoing studies are evaluating whether the rate of loss of F-Dopa or β-CIT differs in response to several putative neuroprotective or restorative therapies. These studies will further elucidate the use of neuroreceptor imaging as a biomarker or surrogate end point for disease progression. As genetic and environmental at-risk groups for PD are identified, imaging studies will also be crucial in establishing the onset of neurodegeneration and whether potential protective treatments are effective even prior to symptoms. In a slowly, but variably, progressive neurodegenerative disorder like PD, imaging may be particularly useful in establishing at-risk groups for rapid or slow progression of disease and assessing therapies directed at each group. As we are poised on the brink of new protective and restorative therapies for PD, neuroimaging offers the potential to provide an objective end point for therapeutic trials on disease progression.

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