Objectives: To examine the validity of [[I.sup.123]][beta]-CIT SPECT for monitoring the progression of dopaminergic degeneration in Parkinson's disease; to investigate the influence of short term treatment with [D.sub.2] receptor agonists on striatal [[I.sup.123]][beta]-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 [[I.sup.123]][beta]-CIT binding to the striatum, putamen, and caudate nucleus was used as the outcome measure.
Results: A decrease in [[I.sup.123]][beta]-CIT binding ratios between the two images was found in all regions of interest. The average decrease in [[I.sup.123]][beta]-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 [[I.sup.123]][beta]-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: [[I.sup.123]][beta]-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in Parkinson's disease and may provide an objective method of measuring the effectiveness of neuroprotective treatments. Short term treatment with a [D.sub.2] agonist does not have a significant influence on [[I.sup.123]][beta]-CIT binding to dopamine transporters. If the latter finding is replicated in larger groups of patients, it supports the suitability of [[I.sup.123]][beta]-CIT SPECT for examining the progression of neurodegeneration in patients being treated with [D.sub.2] receptar agonists.
The pathophysiological hallmark of Parkinson's disease is a slow, progressive degeneration of dopaminergic neurones in the substantia nigra. (1) Standard therapeutic interventions are aimed at replenishing empty dopamine stores with levodopa, or substitution with dopamine receptor agonists. However, in the long term this symptomatic treatment fails. Various neuroprotective agents are currently being developed with the intention of treating the cause of the disease and thereby delaying the degeneration of dopaminergic neurones. To evaluate the effectiveness of such agents, it is important to develop methods that can reliably measure progression of dopaminergic degeneration. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) could prove to be objective tools for measuring the effectiveness of putative neuroprotective agents and monitoring disease progression. For example, recent studies using [[F.sup.18]]dopa PET have shown that the presynaptic dopaminergic degeneration in Parkinson's disease is faster than in normal aging. (2-4)
Since 1993, [[I.sup.123]][beta]-CIT SPECT has been used to investigate the presynaptic dopaminergic system in Parkinson's disease by assessing the concentration of striatal dopamine transporters. Several studies have shown that decreased striatal [[I.sup.123]][beta]-CIT binding correlates well with symptom severity. (5,6) [[I.sup.123]][beta]-CIT SPECT is now considered a highly reproducible technique which could be of value in monitoring the progression of dopaminergic degeneration in Parkinson's disease. (7,8)
Our aim in this study was to investigate whether serial [[I.sup.123]][beta]-CIT SPECT imaging can be used as a marker of Parkinson's disease progression. We undertook two [[I.sup.123]][beta]-CIT SPECT imaging series 12 months apart in a group of 50 patients with early stage Parkinson's disease, We also estimated the sample size and scan interval necessary to predict the effectiveness of a putative neuroprotective agent.
For the "progression study," a group of 50 patients with Parkinson's disease (31 men and 19 women) was examined by clinical assessment and [[I.sup.123]][beta]-CIT SPECT imaging. The patients were recruited from the movement disorders unit of our outpatient clinic. The diagnosis of Parkinson's disease was established according to the UK Parkinson's Disease Society brain bank criteria. (9) The mean (SD) age of the patients at the time of the first imaging was 56.7 (9.3) years, range 37 to 71. The mean duration of Parkinson's disease was 2.7 (2.2) years. The Hoehn and Yahr staging scale (10) and the unified Parkinson's disease rating scale (UPDRS) (11) were used to assess the stage and severity of the disease at the time of first imaging. A detailed clinical and demographic description is given in table 1. Each patient was imaged on two occasions, with a mean scan to scan interval of 51 (7) weeks.
All patients gave written informed consent to the research protocol, which was approved by the medical ethics committee of the hospital.
Drug treatment …