Additional Role of Midbrain F-18 FP-CIT Uptake on PET in Evaluation
of Essential Tremor and Parkinsonism
Authors: Hwang Kyung-Hoon , Lee Haejun , Sung Young Hee 
Published: February 2023

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 definitive diagnosis, it could provide another piece of information and specific diagnostic guidelines for the differentiation of parkinsonism.