• Parkinson’s disease
• SPECT
• PET

A persisting frustration in the diagnosis, treatment, and research of Parkinson’s disease is the lack of an objective measure of the nigrostriatal dopaminergic deficit. In particular, we need a tool to monitor the progress of the neuronal degeneration. This is very difficult to achieve clinically in Parkinson’s disease because of the complex clinical presentation and the confounding effect of symptomatic therapy. Although PET, with markers of presynaptic dopaminergic function such as 6-fluorodopa, is an accepted measuring tool, PET is complex, expensive, cumbersome, and not widely available. The alternative is SPECT, and Winogrodzka et al on pp 294–298¹ of this issue provide evidence that SPECT does the job.

Winogrodzka et al took 50 patients with Parkinson’s disease and performed SPECT scans 12 months apart. For their tracer, they chose [¹²³I] β-CIT, which binds to the presynaptic dopamine transporters. They showed an 8% decline in binding density. This matches well with previous PET, SPECT, and clinical studies.²

Why is this important? Because we may soon have agents that slow the underlying progression of Parkinson’s disease. Animal studies suggest that dopamine agonists, particularly the new ones, may be neuroprotective. A recent paper has suggested that Coenzyme Q10 may also slow neurodegeneration.³ Before we can accept these exciting possibilities, we need objective evidence for a slowing of loss of dopaminergic function. Winogrodzka et al have calculated from their SPECT data that a 30% protective effect over 2 years could be shown with 216 patients in the treatment and control groups. This would be a large but possible study.

Before we accept the results of SPECT and PET studies of neuroprotective therapy for Parkinson’s, more work must be done. In particular, it is theoretically possible for an agent such as a dopamine agonist to change the density of the presynaptic dopamine transporters. This would give a false impression that the agent was altering the number of dopaminergic neurones. Winogrodzka et al showed no effect of agonist therapy in a subgroup of patients, but the number of subjects was too low to draw a firm conclusion. Their findings are in agreement with other short term studies, but we still do not have a definitive answer to the question. We are starting to see the results of imaging studies of possible neuroprotective agents.⁴ The question of the therapeutic agent changing the tracer binding must be answered before we can interpret with confidence the results of imaging studies of neuroprotection for Parkinson’s disease.