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From the Department of Neurology (Dr. Marek and B. Fussell), Psychiatry (Drs. Innis and van Dyck), and Diagnostic Radiology (Dr. Seibyl and M. Early), Yale University School of Medicine, New Haven, CT; and Department of Biostatistics (Drs. Oakes and Eberly), University of Rochester, NY.
Address correspondence and reprint requests to Dr. Kenneth Marek, The Institute for Neurodegenerative Disorders, 60 Temple Street, Suite 8B, New Haven, CT 06510; e-mail: kmarek{at}indd.org
Background:— [123I]ß-CIT and SPECT imaging of the dopamine transporter is a sensitive biomarker of PD onset and severity.
Objective:— In this study, the authors examine the change in [123I]ß-CIT uptake in sequential SPECT scans to assess the rate of progression of the dopaminergic terminal loss in patients with PD.
Methods:— Patients with PD (n = 32) and healthy controls (n = 24) recruited from the Yale Movement Disorders Center underwent repeat [123I]ß-CIT SPECT imaging during a 1- to 4-year period. The primary imaging outcome was the ratio of specific to nondisplaceable striatal activity. Disease severity was assessed by Hoehn and Yahr staging, and Unified Parkinson Disease Rating Scale after 12 hours off drug.
Results:— Sequential SPECT scans in PD subjects demonstrated a decline in [123I]ß-CIT striatal uptake of approximately 11.2%/year from the baseline scan, compared with 0.8%/year in the healthy controls (p < 0.001). Although [123I]ß-CIT striatal uptake in the PD subjects was correlated with clinical severity, the annual percentage loss of [123I]ß-CIT striatal uptake did not correlate with the annual loss in measures of clinical function.
Conclusions:— The rate of dopaminergic loss in PD is significantly greater than that of healthy controls, and [123I]ß-CIT SPECT imaging provides a quantitative biomarker for the progressive nigrostriatal dopaminergic degeneration in PD. As new protective and restorative therapies for PD are developed, dopamine transporter imaging offers the potential to provide an objective endpoint for these therapeutic trials.
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