dopaminergic degeneration in early stage Parkinson's disease

123 I)β-CIT binding; and to determine the sample size and frequency of SPECT imaging required to demonstrate a significant effect of a putative neuroprotective agent. Methods: A group of 50 early stage Parkinson's disease patients was examined. Two SPECT imaging series were obtained, 12 months apart. The mean annual change in the ratio of specific to non-specific ( 123 I)β-CIT binding to the striatum, putamen, and caudate nucleus was used as the outcome measure. Results: A decrease in ( 123 I)β-CIT binding ratios between the two images was found in all regions of interest. The average decrease in ( 123 I)β-CIT binding ratios was about 8% in the whole striatum, 8% in the putaminal region, and 4% in the caudate region. Comparison of scans done in nine patients under two different conditions—in the off state and while on drug treatment—showed no significant alterations in the expression of striatal dopamine transporters as measured using ( 123 I)β-CIT SPECT. Power analysis indicated that to detect a significant (p < 0.05) effect of a neuroprotective agent with 0.80 power and 30% of predicted protection within two years, 216 patients are required in each group when the effects are measured in the whole putamen. Conclusions: (

[1]  Douglas G. Altman,et al.  Practical statistics for medical research , 1990 .

[2]  Jan Booij,et al.  Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism , 1999, European Journal of Nuclear Medicine.

[3]  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.

[4]  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.

[5]  D. Brooks The early diagnosis of parkinson's disease , 1998, Annals of neurology.

[6]  M. Fujita,et al.  Comparison between the decrease of dopamine transporter and that of L‐DOPA uptake for detection of early to advanced stage of Parkinson's disease in animal models , 1999, Synapse.

[7]  J B Habraken,et al.  Imaging of dopamine transporters with iodine-123-FP-CIT SPECT in healthy controls and patients with Parkinson's disease. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  M Schulzer,et al.  Longitudinal fluorodopa positron emission tomographic studies of the evolution of idiopathic parkinsonism , 1994, Annals of neurology.

[9]  H N Wagner,et al.  In vivo imaging of dopamine reuptake sites in the primate brain using single photon emission computed tomography (SPECT) and iodine‐123 labeled RTI‐55 , 1992, Synapse.

[10]  V. Sossi,et al.  In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease , 2000, Annals of neurology.

[11]  J. Meador-Woodruff,et al.  Lack of dopamine receptor agonists effect on striatal dopamine transporter binding sites , 1996, Brain Research.

[12]  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.

[13]  J. Hughes,et al.  Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. , 1992, Journal of neurology, neurosurgery, and psychiatry.

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

[15]  P B Hoffer,et al.  Test/retest reproducibility of iodine-123-betaCIT SPECT brain measurement of dopamine transporters in Parkinson's patients. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[16]  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.

[17]  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.

[18]  K. Frey,et al.  The vesicular monoamine transporter is not regulated by dopaminergic drug treatments. , 1995, European journal of pharmacology.

[19]  M. Kaufman,et al.  Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson's‐diseased striatum , 1991, Synapse.

[20]  D. Charney,et al.  Age-Related Decline in Striatal Dopamine Transporter Binding with Iodine-123-β-CITSPECT , 1995 .

[21]  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.

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

[23]  H. Kung,et al.  Pharmacological effects of dopaminergic drugs on in vivo binding of [99mTc]TRODAT-1 to the central dopamine transporters in rats , 1997, European Journal of Nuclear Medicine.

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

[25]  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.

[26]  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.

[27]  Marc Laruelle,et al.  SPECT imaging of dopamine and serotonin transporters with [123I]β‐CIT: Pharmacological characterization of brain uptake in nonhuman primates , 1993, Synapse.

[28]  J. C. Stoof,et al.  [123I]β-CIT single-photon emission tomography in Parkinson's disease reveals a smaller decline in dopamine transporters with age than in controls , 1997, European Journal of Nuclear Medicine.

[29]  Willibald Gerschlager,et al.  Progression of dopaminergic degeneration in Parkinson's disease and atypical parkinsonism: A longitudinal β‐CIT SPECT study , 2002, Movement disorders : official journal of the Movement Disorder Society.

[30]  J. Booij,et al.  [123I]FP-CIT SPECT is a useful method to monitor the rate of dopaminergic degeneration in early-stage Parkinson's disease , 2001, Journal of Neural Transmission.

[31]  J. C. Stoof,et al.  Drug-naive patients with Parkinson’s disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [123I]β-CIT SPECT , 1997, Journal of Neurology.