Objective: This study aimed to visualize α-synuclein aggregates in living patients with Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).

Background: We developed an imaging probe, [¹⁸F]C05-05, for α-synuclein inclusions and demonstrated its in-vivo performance as a PET tracer in animal models[1]. Here, we report the first-in-human evaluation of [¹⁸F]C05-05 in PD, DLB, and MSA cases compared to healthy controls (HCs).

Method: Participants

Four patients with PD, one with DLB, three with MSA-P, and five HCs were recruited. All subjects were Aβ-negative according to visual inspection of [¹¹C]PiB-PET images.

Image analysis

Standardized uptake value ratio (SUVR) images were generated from PET images at 100–120 min after [¹⁸F]C05-05 injection using cerebral deep white matter (superior corona radiata and posterior corona radiata) as a reference region. Regions of interest (ROIs) for quantitative analysis were automatically segmented from 3D T1-weighted images using the M-vision brain tool.

Results: MSA cases showed prominent radiosignal accumulations in the basal ganglia and/or middle cerebellar peduncle, similar to a previous observation with a different probe[2]. In PD and DLB, collectively referred as Lewy body diseases (LBDs), enhanced retention of [¹⁸F]C05-05 was noted around the substantia nigra according to visual reads of images. Correspondingly, ROI-based quantifications showed that the radioprobe SUVR in the substantia nigra was significantly higher in LBD patients than in the HCs. In addition, there was a significant positive correlation between the severity of motor symptoms assessed by MDS-UPDRS part III and nigral SUVRs in the LBD group.

Conclusion: Our findings support the capability of [¹⁸F]C05-05 for capturing α-synuclein aggregates in not only MSA but LBDs.

References: [1] M Ono, M Takahashi, A Shimozawa, et al., In vivo visualization of propagating α-synuclein pathologies in mouse and marmoset models by a bimodal imaging probe, C05-05. bioRxiv. 2020 DOI: 10.1101/2020.10.23.349860 PPR: PPR229812
[2] K Matsuoka, M Ono, Y Takado, et al., High-Contrast Imaging of α-Synuclein Pathologies in Living Patients with Multiple System Atrophy. Mov Disord. 2022 DOI: doi.org/10.1002/mds.29186

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pet-visualization-of-%ce%b1-synuclein-pathologies-in-humans-using-18fc05-05/