[123I]β-CIT SPECT imaging assessment of the rate of Parkinson’s disease progression

Background: [123I]β-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]β-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]β-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]β-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]β-CIT striatal uptake in the PD subjects was correlated with clinical severity, the annual percentage loss of [123I]β-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]β-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.

[1]  S J Kish,et al.  [11C]RTI‐32 PET studies of the dopamine transporter in early dopa‐naive Parkinson's disease , 1997, Neurology.

[2]  S H Snyder,et al.  Positron emission tomographic imaging of the dopamine transporter with 11C‐WIN 35,428 reveals marked declines in mild Parkinson's disease , 1993, Annals of neurology.

[3]  S. Fahn Members of the UPDRS Development Committee. Unified Parkinson's Disease Rating Scale , 1987 .

[4]  J. Rinne,et al.  Progression in Parkinson's disease: A positron emission tomography study with a dopamine transporter ligand [18F]CFT , 2000, Annals of neurology.

[5]  P. Morrish Parkinson's disease is not a long‐latency illness , 1997, Movement disorders : official journal of the Movement Disorder Society.

[6]  N. Alpert,et al.  Rapid detection of Parkinson's disease by SPECT with altropane: A selective ligand for dopamine transporters , 1998, Synapse.

[7]  R. Roth,et al.  Novel Radioligands for the Dopamine Transporter Demonstrate the Presence of Intrastriatal Nigral Grafts in the MPTP-Treated Monkey: Correlation with Improved Behavioral Function , 1994, Experimental Neurology.

[8]  L. Deecke,et al.  Imaging of dopamine transporters with iodine-123-beta-CIT and SPECT in Parkinson's disease. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[9]  M. Brin,et al.  Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. , 1993, The New England journal of medicine.

[10]  I. Shoulson,et al.  Experimental therapeutics of neurodegenerative disorders: unmet needs. , 1998, Science.

[11]  A. Lees,et al.  Ageing and Parkinson's disease: substantia nigra regional selectivity. , 1991, Brain : a journal of neurology.

[12]  J D Speelman,et al.  [123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease. , 1997, Journal of neurology, neurosurgery, and psychiatry.

[13]  D. Brooks,et al.  A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. , 2000, The New England journal of medicine.

[14]  Eileen O. Smith,et al.  Decreased single‐photon emission computed tomographic {123I}β‐CIT striatal uptake correlates with symptom severity in parkinson's disease , 1995, Annals of neurology.

[15]  Haruhiko Akiyama,et al.  Rate of cell death in parkinsonism indicates active neuropathological process , 1988, Annals of neurology.

[16]  W. Koller,et al.  The next frontier in Parkinson's disease , 1991, Neurology.

[17]  J. P. Seibyl,et al.  [sup 123 I] beta-CIT/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson's disease , 1996, Neurology.

[18]  D. Maraganore,et al.  The effect of dopamine agonist therapy on dopamine transporter imaging in Parkinson's disease , 1999, Movement disorders : official journal of the Movement Disorder Society.

[19]  Robert B. Innis,et al.  Graphical, Kinetic, and Equilibrium Analyses of in vivo [123I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[20]  J. Seibyl,et al.  Effect of treatment with L‐dopa/carbidopa or L‐selegiline on striatal dopamine transporter SPECT imaging with [123I]β‐CIT , 1999, Movement disorders : official journal of the Movement Disorder Society.

[21]  J S Fowler,et al.  Decreased dopamine transporters with age in healthy human subjects , 1994, Annals of neurology.

[22]  D B Calne,et al.  Is idiopathic parkinsonism the consequence of an event or a process? , 1994, Neurology.

[23]  M. Schiess,et al.  Immediate-release and controlled-release carbidopa/levodopa in PD: A 5-year randomized multicenter study. , 2000, Neurology.

[24]  D J Brooks,et al.  An [18F]dopa-PET and clinical study of the rate of progression in Parkinson's disease. , 1996, Brain : a journal of neurology.

[25]  J. Jankovic,et al.  Variable expression of Parkinson's disease , 1990, Neurology.

[26]  D. Brooks,et al.  Core assessment program for intracerebral transplantations (CAPIT) , 1992, Movement disorders : official journal of the Movement Disorder Society.

[27]  Robert B. Innis,et al.  Evaluation of the monoamine uptake site ligand [131I]methyl 3β-(4-Iodophenyl)-tropane-2β-carboxylate ([123I]β-CIT) in non-human primates: Pharmacokinetics, biodistribution and SPECT brain imaging coregistered with MRI , 1993 .

[28]  S Fahn,et al.  Parkinson disease, the effect of levodopa, and the ELLDOPA trial. Earlier vs Later L-DOPA. , 1999, Archives of neurology.

[29]  D J Brooks,et al.  Clinical and [18F] dopa PET findings in early Parkinson's disease. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[30]  M Laruelle,et al.  Single photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters in Parkinson disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[31]  S. Kish,et al.  Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. , 1988, The New England journal of medicine.

[32]  M. Hoehn,et al.  Parkinsonism , 1967, Neurology.

[33]  K. Jellinger,et al.  Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. , 1973, Journal of the neurological sciences.

[34]  J S Rakshi,et al.  Measuring the rate of progression and estimating the preclinical period of Parkinson’s disease with [18F]dopa PET , 1998, Journal of neurology, neurosurgery, and psychiatry.

[35]  J. Kleinman,et al.  Decreased density of human striatal dopamine uptake sites with age. , 1986, European Journal of Pharmacology.

[36]  R. Mayeux,et al.  Does a long preclinical period occur in Parkinson's disease? , 1991, Neurology.

[37]  Lee-Tzuu Chang,et al.  A Method for Attenuation Correction in Radionuclide Computed Tomography , 1978, IEEE Transactions on Nuclear Science.