Preserved Serotonin Transporter Availability in Parkinson Disease Measured with Either [¹¹C]MADAM or [¹¹C]DASB: A Study Including 2 Separate Cohorts of Nondepressed Patients

Abstract

Serotonin transporter (SERT) availability was assessed using 2 tracers, [¹¹C]N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ([¹¹C]DASB) and [¹¹C]N,N-dimethyl-2-(2-amino-4-fluoromethylphenylthio)benzylamine) ([¹¹C]MADAM), in independent cohorts of patients and controls. This study aimed to independently confirm whether SERT remains intact in nondepressed individuals with early-stage Parkinson disease (PD), because the use of diverse methodologies could potentially yield disparate results. Methods: Seventeen PD patients (5 women and 12 men; age, 64 ± 7 y; Unified Parkinson’s Disease Rating Scale motor score, 23 ± 5; Beck Depression Inventory score, 5 ± 4) and 20 age- and sex-matched healthy controls underwent [¹¹C]MADAM PET at Karolinska Institutet. Fifteen PD patients (5 women and 10 men; age, 59 ± 9 y; Unified Parkinson’s Disease Rating Scale motor score, 15 ± 7; Beck Depression Inventory score, 4 ± 4) and 8 controls were examined with [¹¹C]DASB PET at the University of British Columbia. PET scans were performed at both institutions using a high-resolution research tomograph. A simplified reference tissue model and Logan graphical analysis were used to calculate the regional nondisplaceable binding potential (BP_ND), using the cerebellum as the reference. Parametric BP_ND images were generated using wavelet-aided parametric imaging. MRI-defined volumes of interest included cortical and subcortical regions, as well as brain stem nuclei. Results: There were no significant differences between controls and early-stage PD patients in either the [¹¹C]DASB or the [¹¹C]MADAM cohort, regardless of the analysis method. Group differences (Cohen d) in the [¹¹C]DASB cohort ranged from 0.34 to 0.86 in brain stem nuclei, 0.09 to 0.61 in subcortical regions, and 0.28 to 0.70 in cortical regions. In the [¹¹C]MADAM cohort, they ranged from 0.16 to 0.40, 0.19 to 0.55, and 0.32 to 0.61, respectively. Logan BP_ND highly correlated with simplified reference tissue model BP_ND for both tracers in each group (P < 0.001). Conclusion: SERT availability is relatively preserved in nondepressed patients with PD. This study suggests that serotonergic degeneration is not a major feature of the disease in nondepressed patients with nonadvanced disease.