Striatal [11C]dihydrotetrabenazine and [11C]methylphenidate binding in Tourette syndrome

Abstract

Objective: Tourette syndrome (TS) is a common neurodevelopmental disorder marked by tics and behavioral comorbidities. Clinical pharmacology suggests that dopaminergic signaling abnormalities are part of the pathophysiology of TS. Prior molecular imaging studies of nigrostriatal dopaminergic terminal markers report conflicting results. Our goal was to characterize the distribution of nigrostriatal dopaminergic terminals in subjects with TS.

Methods: Thirty-three adult subjects with TS were studied with PET using [11C]dihydrotetrabenazine (DTBZ), a ligand for the type 2 vesicular monoamine transporter, and with [11C] methylphenidate (MP), a ligand for the plasmalemmal dopamine transporter. Subjects were characterized with standard rating instruments for tic severity, obsessive-compulsive behaviors, and attentional deficits.

Results: We found no differences between subjects with TS and control subjects in DTBZ and MP binding in any striatal region. There was no correlation between binding measures and clinical variables. Ventral striatal DTBZ and MP binding distributions in subjects with TS were normal.

Conclusions: We found no evidence of increased striatal dopaminergic innervation in Tourette syndrome (TS). Discrepancy between our present results and those of other studies may be explained by heterogeneity of TS.

Figure 1 Average parametric images of [¹¹C]DTBZ and [¹¹C]MP binding in Tourette syndrome (TS) and normal control (NC) subjects Six brain levels through the striatum for both controls (first and fourth rows) and subjects with TS (second and fifth rows) for DTBZ (top) and MP (bottom). Each slice represents the average DVR of the entire subject group (NC = 28, TS = 33). Subtraction images of TS minus control (third and sixth rows) with modest increases in some voxels in TS ventral striatum.

Figure 2 Scatterplots of [¹¹C]DTBZ and [¹¹C]MP binding in Tourette syndrome and control ventral striatum DTBZ = [¹¹C]dihydrotetrabenazine; DVR = ratio of volumes of distribution; MP = [¹¹C]methylphenidate.