Iodine-123-epidepride-SPECT: studies in Parkinson's disease, multiple system atrophy and Huntington's disease

Epidepride is a benzamide derivative with very high affinity for D2 receptors, which, in its [123I]-labeled form, can be used for SPECT. The aim of this study was to evaluate the usefulness and accuracy of [123I]epidepride-SPECT for the differential diagnosis of movement disorders.

SPECT imaging with a triple-headed scintillation camera was performed in 9 patients with Parkinson's disease, 9 patients with probable multiple system atrophy (MSA), 1 patient with progressive supranuclear palsy, 16 patients with Huntington's disease (HD) and 14 controls, 3 hr after the intravenous injection of 3.7 +/- 1.3 mCi of [123I]epidepride. The striatum-to-cerebellum ratio - 1, reflecting the specific-to-nondisplaceable binding ratio, was used as a semiquantitative measure of D2 receptor binding.

Kinetic studies showed peak striatal uptake about 3 hr postinjection and a slow decline thereafter. The striatum-to-cerebellum ratio - 1 was significantly reduced in MSA (11.8 +/- 3.9, compared to controls, 19.0 +/- 6.3; p < 0.01) and in patients with HD (8.8 +/- 3.2; p < 0.00005) but normal in Parkinson's disease (15.8 +/- 3.6; not significant). A high interindividual variation of specific striatal epidepride binding (striatum - cerebellum; cpm/mCi x kg) was found in controls and in all patient groups. The interindividual variation of striatum-to-cerebellum ratios was lower but still considerable. In half of the MSA patients, the specific-to-nondisplaceable binding ratio fell within the range of controls. The use of various cortical reference regions did not improve discrimination between MSA and controls or Parkinson's disease patients, respectively. The discrimination of HD patients from controls was better, with overlap in only two cases. In one HD patient, calculation of the striatum-to-cerebellum ratio was almost impossible due to extremely low nonspecific binding. Possible explanations for the large variation of the ratios, resulting in an overlap between controls and different patient groups, are very low counting rates in the reference region and the fact that a transient binding equilibrium may not be achieved after bolus injection of epidepride.

Epidepride appears to be a useful SPECT ligand for studying dopamine D2 receptors. However, its markedly higher specific-to-nondisplaceable binding ratio in comparison to those of iodobenzamide or other D2 ligands did not result in a better discrimination between different basal ganglia disorders. The calculation of plasma input curves and volumes of distribution might improve the accuracy of [123I]epidepride-SPECT.