A study of D2/D3 dopamine receptor distribution with [¹¹C]PHNO in a rare form of Tourette syndrome

Objectives The goal of the study was to evaluate the distribution of D2/D3 dopamine receptors using [¹¹C]PHNO in members of a family with a Tourette Syndrome (TS) that carries a rare mutation in the L-histidine decarboxylase (HDC) gene, and compare them with gender, age and weight matched healthy controls (HC).

Methods Three members of a family with TS and a mutated HDC gene (2 males, 1 female; age=29±15; BMI=30±5) and 9 healthy controls (6 males, 3 females; age=29±11; BMI=28±7) were included in the study . Each subject underwent one [¹¹C]PHNO scan on a HRRT scanner. Injected activities were 292±129 MBq with a total injected mass of 0.028±0.004 µg/kg (max=0.032 µg/kg). Specific radioactivity was 58±27 MBq/nmol at the end of synthesis and 32±15 MBq/nmol at injection time. Images were reconstructed using the MOLAR algorithm with all corrections, including motion. Regions of interest were delineated in the cerebellum, caudate, putamen, pallidum and substantia nigra. Binding potentials were quantified using cerebellum as the reference region and SRTM.

Results [¹¹C]PHNO binding potentials (BPND) estimated with SRTM were higher in the caudate (+11%), putamen (+19%) and pallidum (+48%), but not significantly, and more markedly in the substantia nigra (+139%, p≤0.01, Mann-Whitney rank-sum test) for members of the TS family as compared to HCs.

Conclusions [¹¹C]PHNO is a dopamine receptor radioligand that binds to both D2 and D3 subtypes with a higher affinity for the D3 subtype (approx. 30-50 fold). Since most of [¹¹C]PHNO BPND in the substantia nigra (and majority in the pallidum) is due to the contribution of the D3 subtype, the observed increase may be due to changes in D3. Further studies would be useful to investigate whether the observed effect is linked to the rare mutation, or if it can also be found in patients with idiopathic TS.

Research Support This study was funded in part by NARSAD and NIDA grants