Objective: The aim of this study is to investigate the influence of the intensity of dopaminergic projections to the ventral striatum (VS) measured with F-18-DOPA-PET in the development of impulse control disorders (ICDs) in patients with Parkinson’s disease (PD).

Background: ICDs including gambling, hypersexuality etc. are a frequent side effect of dopamine replacement therapy in patients with PD. Cilia et al. and others have shown that ICD patients show a reduced signal in FP-CIT-SPECT in the VS, reflecting either a reduction of mesolimbic projections or, alternatively, a lower membrane dopamine transporter (DAT) expression on presynaptic terminals.

Methods: 59 participants, 46 of which with PD underwent a 90 minute dynamic F-18-DOPA-PET scan. Scans were spatially normalized to a DOPA-PET-template (García-Gomez et al, 2013) using SPM12. Patlak slopes (Ki) for each voxel were calculated with a custom built script using the occipital cortex as reference region. Ki in 7 striatal regions derived from the FSL striatum connectivity atlas were extracted. All participants completed the QUIP-RS questionnaire, a well-validated test to detect and quantify ICD behavior in PD (Probst et al., 2014).

Results: 17 Patients had a QUIP-RS score of greater than 8 and were therefore classified as having an ICD. In this group, a negative correlation was found between average Ki and QUIP-RS score in regions connected to the limbic system, i.e. mainly the VS (r=-0.52, p=0.03) and in regions connected to the executive system, i.e. the rostral caudate nucleus (r= -0.60, p=0.01). Similar results could be obtained by analyzing the static time frame from 80-90 minutes using the same reference region.

Conclusions: PD patients with symptoms of ICD show decreased F-18-DOPA-PET signal in the VS and the rostral caudate nucleus. The intensity of PET signal reduction in these regions correlated well with the severity of ICD symptoms. We conclude that a reduction in dopaminergic projections to the striatum rather than a functional downregulation of DAT could be responsible for the development of ICDs.

References: Cilia R1, Ko JH, Cho SS, van Eimeren T, Marotta G, Pellecchia G, Pezzoli G, Antonini A, Strafella AP. Reduced dopamine transporter density in the ventral striatum of patients with Parkinson’s disease and pathological gambling. Neurobiol Dis. 2010 Jul;39(1):98-104 García-Gómez FJ, García-Solís D, Luis-Simón FJ, Marín-Oyaga VA, Carrillo F, Mir P, Vázquez-Albertino RJ. Elaboration of the SPM template for the standardization of SPECT images with 123I-Ioflupane. Rev Esp Med Nucl Imagen Mol. 2013 Nov-Dec;32(6):350-6

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MDS Abstracts - https://www.mdsabstracts.org/abstract/f-18-dopa-pet-predicts-impulsive-behavior-under-dopaminergic-therapy-in-parkinson-patients/