Objective: To establish a method for evaluating midbrain accumulation of ¹²³I-FP-CIT SPECT and assess its ability to differentiate between Parkinson’s disease (PD) and Parkinsonian syndromes (PS).

Background: ¹²³I-FP-CIT has been reported to bind not only to the striatum but also to the brainstem, with reduced accumulation observed in both regions in PD and PS [1,2]. Visual assessment of brainstem accumulation of ¹²³I-FP-CIT may be useful for the differential diagnosis between PD and PS [3]. However, a semi-quantitative evaluation method has not yet been established.

Method: The quantification of ¹²³I-FP-CIT accumulation was verified using a striatum-midbrain phantom. To calculate relative accumulation of ¹²³I-FP-CIT compared to background accumulation (the midbrain index: MI), fixed and variable volume-of-interest (VOI) regions were defined on the midbrain using either structural brain CT images or SPECT images. The reference background regions included the cerebral cortex, occipital lobe, and cerebellum, and the MI was calculated under each condition. ¹²³I-FP-CIT SPECT images of patients with PD (n=32) and PS (n=10 with multiple system atrophy, n=10 with progressive supranuclear palsy) were analyzed to evaluate the ability of the calculated MI to differentiate between the diseases.

Results: The results of the phantom experiments showed that the striatal accumulation value did not affect the quantification of midbrain accumulation. The MI was consistently lower in the PS than in the PD, regardless of the calculation conditions. The area under the ROC curve (AUC) for differentiating PD from PS was most optimized at 0.75 (p=0.003) when using SPECT image-based VOI positioning, variable VOI, and the cerebellum as the reference background. In contrast, when based on striatal accumulation, the AUC was 0.618 (p=0.259). In PD, MI did not correlate with clinical symptom severity and exhibited independent behavior from degree of striatal degeneration.

Conclusion: The MI derived from ¹²³I-FP-CIT SPECT imaging provides a semi-quantitative method for evaluating brainstem accumulation, which is useful for differentiating PD from PS. This method may offer valuable diagnostic insights, especially when striatal accumulation alone lacks sufficient diagnostic accuracy. Further studies are needed to validate these findings and explore the potential clinical applications of this semi-quantitative approach.

References: [1] Roselli F, Pisciotta NM, Pennelli M, et al. Midbrain SERT in degenerative parkinsonisms: a 123I-FP-CIT SPECT study. Mov Disord. 2010;25(12):1853-1859. doi:10.1002/mds.23179
[2] Nicastro N, Fleury V, Broc N, et al. Extrastriatal 123I-FP-CIT SPECT impairment in degenerative parkinsonisms. Parkinsonism Relat Disord. 2020;78:38-43. doi:10.1016/j.parkreldis.2020.07.008
[3] Totsune T, Baba T, Sugimura Y, et al. A proposal of visual assessment of serotonergic deficits in parkinsonian syndromes: An 123I-FP-CIT SPECT study. Brain Disorders. 2025;17:100192. doi: 10.1016/j.dscb.2025.100192

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MDS Abstracts - https://www.mdsabstracts.org/abstract/semi-quantitative-evaluation-of-midbrain-accumulation-in-123i-fp-cit-spect-in-parkinsons-disease-and-parkinsonian-syndromes/