Additional Role of Midbrain F-18 FP-CIT Uptake on PET in Evaluation of Essential Tremor and Parkinsonism

Abstract

Background: Parkinsonism is a term used for the collection of clinical features that cause movement disorders similar to those in Parkinson's disease. Accurate differentiation of these disorders is critical for the treatment and prognosis of any disease. Fluorine-18 N-(3-fluoropropyl)-2β- carboxymethoxy-3β-(4-iodophenyl) nortropane (F-18 FP-CIT) has been used in the evaluation of parkinsonism by its uptake in the dopamine active transporter (DAT) of the striatum. Its uptake in other areas of the brain, such as serotonin transporter (SERT) in the midbrain or thalamus, is also recognised.

Objective: To investigate whether midbrain SERT uptake of F-18 FP-CIT on positron emission tomography (PET) could be applied to the differentiation of parkinsonism in combination with striatal DAT uptake.

Methods: This retrospective study included clinically diagnosed three essential tremors (ET), 53 parkinsonism patients (21 idiopathic Parkinson's disease (IPD), 6 multiple system atrophy - cerebellar type (MSA-C), 7 multiple system atrophy - parkinsonian type (MSA-P), 8 vascular parkinsonism (VP), and 11 drug-induced parkinsonism (DIP)), and 16 healthy controls. The patient group consisted of 29 men and 27 women (age mean ± SD years, 69.9 ± 8.5 and 69.2 ± 8.9, respectively), and the healthy controls consisted of 8 men and 8 women (age mean ± SD years, 64.5 ± 8.2 and 64.3 ± 7.6, respectively). Mean standardized uptake values (SUVs) and activity volumes were measured from the visualized FP-CIT uptake of the midbrain (substantia nigra and dorsal raphe nucleus) as well as the striatum (caudate nucleus and putamen). The mean SUVs of the occipital region were measured as the background activity. The semiquantitative binding ratio (BR) was calculated using the following formula: BR = (SUVmean of the region of interest - SUVmean of background)/SUVmean of the background. SUV, volume, and BR in each type of parkinsonism were compared with those in healthy controls using both nonparametric and parametric methods. The correlation between the visual score of the qualitative analysis and the BR was examined.

Results: Except for the dorsal raphe nucleus in VP, the midbrain BRs in all parkinsonism showed a statistically significant decrease compared to those in healthy controls. Both midbrain and striatal BRs were significantly decreased only in patients with IPD or MSA-P; a greater decrease of substantia nigra BR was identified in MSA-P than in IPD (p < 0.05). The striatal BRs in MSA-C, VP, and DIP showed no significant difference from those in healthy controls. Finally, four patterns of uptake were identified: 1) decreased striatal and midbrain uptake for IPD and MSA-P, 2) normal striatal uptake and decreased midbrain uptake (both substantia nigra and dorsal raphe nucleus) for MSA-C and DIP, 3) normal striatal uptake and decreased substantia nigra uptake (without decreased dorsal raphe nucleus uptake) for VP, and 4) normal striatal and midbrain uptake for ET.

Conclusion: The possible differential diagnoses were split into two groups when only striatal uptake was considered but they were divided into four groups after adding midbrain uptake. Although additional midbrain F-18 FP-CIT uptake still could not make a final definitive diagnosis, it could provide another piece of information and specific diagnostic guidelines for the differentiation of parkinsonism.

Keywords: F-18 FP-CIT; Midbrain; differentiation; dopamine transporter; parkinsonism; serotonin transporter; uptake.