Quantification of receptor function in patients with movement disorders

Dr George Larcos (Chief Investigator) Professor Brian Hutton, Rochelle Hatton, Mohammed Shaffi, Dr Victor S C Fung, Associate Professor John Morris (Co-Investigators), Mariese Hely, Andrew Katsifis, Westmead Hospital

Damage to brain cells in Parkinson's disease results in lack of the brain chemical dopamine. This results in the motor symptoms that affect people with Parkinson's disease: tremor, stiffness, slowed movement and impaired walking and balance. Currently diagnosis of Parkinson's disease relies almost solely on clinical assessment. With the support of the Brain Foundation, we are using radionuclide imaging of the brain with recently developed compounds which label dopamine channels and receptors in order to objectively assess dopamine function in Parkinsons's disease and related conditions.

Our aim is to develop reliable diagnostic tools to confirm Parkinson's disease and differentiate it from similar conditions. This will allow more accurate diagnosis for patients and more rational and targeted treatment. To date, around 25 patients and normal volunteers have been scanned. We aim to scan around 50-60 subjects all up in the study.

Radiolabelled compounds are available which permit imaging of the receptor distribution in the brain using single photon emission tomography (SPECT). Two of these agents can be used to distinguish between Parkinson’s disease and other movement disorders, where the pattern of uptake in central brain structures differs.

Our goal has been to assess if quantitative analysis can aid in the identification and stratification of disease. Methods have been developed to quantify the uptake of radioactive tracer in the central brain structures compared to elsewhere in the brain. Various parameters have been estimated including the absolute concentration of tracer, the ratio of tracer specifically bound to D2 receptors versus non-specific uptake and the relative volume of the central brain structures.

Work is in progress to assess these parameters in patients at various stages of disease progression compared to normal subjects. Correlation has been demonstrated between some of the parameters and clinical evaluation criteria.

In one subject with clinically undetermined disease the results confirmed Parkinson’s disease (see Figure 1). Preliminary findings are being reported to national meetings in Neurology and Nuclear Medicine.