HAI Book 2025 - Flipbook - Page 101
Capotosti, Francesca
2
From the clinical utility of a-synuclein PET imaging in Multiple System
Atrophy to the possible diagnosis of Parkinson9s disease
Efthymia Vokali1, Jerome Molette1, Diego Rodriguez2, Barbara K. Changizi22, Anastasia
Kuzkina2, Myriam Ravache1, Yannis Dimitrakopoulos1, Christophe Delgado1, Jacqueline
Kocher1, Laure Pittet1, Coralie Vallet1, Valerie Hliva1, Andrea Pfeifer1, Marie Kosco-Vilbois1,
Madiha Derouazi1, Vikram Khurana2, Francesca Capotosti1
1
AC Immune SA, EPFL Innovation Park, Building B, Lausanne, CH
Division of Movement Disorders and Ann Romney Center for Neurologic Diseases, Department of Neurology,
Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, US
2
Parkinson9s disease (PD) and other synucleinopathies, such as Multiple System Atrophy (MSA), involve a
progressive accumulation of a-synuclein (a-syn) inclusions which correlate with clinical manifestations and
disease progression. Imaging a-syn pathology using PET would transform diagnosis, patient recruitment and
monitoring of therapeutic efficacy in clinical trials targeting a-syn. Here, we report new clnical data with [18F]ACI12589 PET together with a skin-biopsy based seed amplification assay (SAA) in MSA.
Eight subjects who met the diagnostic criteria for probable MSA (MSA-P = 5, MSA-C = 3) were enrolled. Subjects
underwent scans 60390 min after injection. PET images were motion-corrected and co-registered to MRI images.
Three 5-mm skin biopsies were obtained in all subjects. The SAA reaction buffer included 1 mg/mL recombinant
³-syn, 10 µM thioflavin T (ThT), and 2µl of 0.5% skin biopsy lysate. Four replicates per sample were incubated at
37°C for 48 hours. Samples were positive if g75% of the replicates crossed the predefined fluorescence threshold.
[18F]ACI-12589 exhibited uptake in the cerebellum all tested MSA-C cases and had a positive SAA signal in 2 out 3
tested cases. Among the five tested probable MSA-P cases, two had a clear uptake in the basal ganglia by PET and
a clear MSA pattern on SAA; one showed a positive MSA signal only by SAA, while the two remaining cases did not
show retention by PET and either a PD pattern in SAA or a consistently negative SAA. Upon clinical re-evaluation,
the diagnosis of those two cases was changed.
While the a-syn [18F]ACI-12589 PET tracer is sufficient for the diagnosis of MSA-C, the combination of both
spatial (PET) and conformational (SAA) a-syn biomarkers could improve the error-prone clinical differential
diagnosis of MSA-P. [18F]ACI-12589 PET tracer alone or in combination with other biomarkers promise to open up
new precision-medicine approaches for this devastating disease.
Keywords: a-synuclein, new tracers, biomarkers
HAI2025 - 101
