Treatment with D-penicillamine improves dopamine D2-receptor binding and T2-signal intensity in de novo Wilson's disease.

We report the results of in vivo striatal dopamine D2-receptor binding assessed by PET using 11C-raclopride (only one patient) and by single-photon emission computed tomography (SPECT) using 123I-iodobenzamide (123I-IBZM) and the findings of T2-weighted MRIs in two de novo Wilson's disease patients before and 4 months after initiation of D-penicillamine treatment. Before treatment, specific 11C-raclopride binding (only patient 1) was markedly reduced, with a putamen to cerebellum ratio of 1.99 (controls: 3.99 +/- 0.55, n = 15) and a caudate to cerebellum ratio of 2.52 (controls: 3.65 +/- 0.59, n = 15). Specific 123I-IBZM binding was reduced in both patients, with a basal ganglia to frontal cortex ratio of 1.25 (patient 1) and of 1.41 (patient 2) controls: 1.57 +/- 0.04, n = 5). After 4 months of therapy, 11C-raclopride-PET improved to a putamen to cerebellum ratio of 2.52 and a caudate to cerebellum ratio of 3.06 (patient 1). 123I-IBZM-SPECT revealed an increase of basal ganglia to frontal cortex ratios of 1.34 (patient 1) and 1.55 (patient 2). On heavily T2-weighted MRI sequences, hyperintense signal changes before therapy within the putamen (both patients), brainstem (only patient 1), and caudate (only patient 2) greatly diminished after treatment. Reduced striatal dopamine D2-receptor binding in these Wilson's disease patients improved under therapy, suggesting, in part, a reversible defect of striatal neurons.