[18F]ACI-15916 PET in α-synucleinopathies

Inclusion Criteria for all Participants: 1. Subject is able to provide written informed consent, which must be obtained before any assessment is performed. 2. Subjects must be able to understand and be willing to comply with study procedures, restrictions, and requirements. 3. Body mass index is \> 18 and \< 31 kg/m2 and Bodyweight ≥ 50 kg and ≤ 100 kg. 4. Female participants must not be of childbearing potential or agree to use highly effective methods of contraception. 5. For subjects receiving arterial cannulation, an adequate circulation to the hand for safe placement of arterial line (as determined by Allen's test). Additional Inclusion Criteria for Healthy Volunteers: 6. Males and females aged ≥ 20 at the time of signing the informed consent. 7. Normal MRI and DAT PET or SPECT (except for Part 4 participants), as judged by the investigator. 8. The subject is, in the opinion of the investigator, generally healthy based on the assessment of medical history, physical examination, vital signs, ECG, and the results of the hematology, clinical chemistry, urinalysis, serology, and other laboratory tests. 9. No family history of α-synucleinopathy, including PD, or other early-onset neurological disease associated with dementia. 10. No personal history of clinically significant neurologic and/or psychiatric disorders. 11. Have a Montreal Cognitive Assessment (MoCA) score ≥ 26 12. No cognitive impairment as judged by the PI or delegated physician. Additional Inclusion Criteria for Participants with α-synucleinopathies: 13. Males and females aged ≥ 40 at the time of signing the informed consent. 14. Subjects diagnosed with any of the following: * Idiopathic PD based on MDS criteria * PD with genetic risk factor (except some mutations as mentioned in exclusion criteria) * Dementia with Lewy bodies (DLB) * Diagnosis of possible or probable Multiple System Atrophy (MSA) 15. Evidence of dopamine transporter deficit on DAT PET or SPECT imaging performed either as part of Screening or previously acquired (if not older than 6 months) and of good quality as judged by the investigator. 16. Medications taken for symptomatic treatment of α-synucleinopathy must be maintained on a stable dosage regimen for at least 30 days before the Screening Visit. Exclusion Criteria for all Participants: 1. Female subjects pregnant, lactating or breastfeeding. 2. Presence of psychiatric symptoms that may interfere with the objectives of the study, as judged by the investigator. 3. Clinically significant concomitant disease or condition within 6 months prior to screening, that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the participant, or compromise the scientific quality of the study. 4. History of brain surgery or any neurosurgical procedures. Subject has received treatment with a drug, antibody or vaccine targeting α-synuclein. 5. Known or suspected drug, alcohol or other abuse, or positive urine drug screen which may interfere with the study objective, as judged by the investigator. 6. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity as judged by the investigator. 7. Subject is involved in the planning and/or conduct of the study (i.e. part of the study team) 8. History of clinically significant cardio-or cerebrovascular, pulmonary, renal, hepatic, neurological, mental or gastrointestinal disorder or any other major disorder that may interfere with the objectives of the study, as judged by the investigator. 9. History of and/or screening brain MRI scan (except for Part 4 subjects) indicative of, clinically significant abnormality including but not limited to prior haemorrhage or infarct or \>3 lacunar infarcts, except changes consistent with α-synucleinopathies for PD, MSA, DLB patients. 10. Subjects being treated with any anticoagulants or antiplatelet drugs, except aspirin at doses of 100 mg daily or lower within 2 weeks of the planned arterial cannula placement (if performed) for either the baseline or retest imaging. 11. Screening supine blood pressure \> 150 mm Hg (systolic) or \> 90 mm Hg (diastolic), following at least 5 minutes of supine rest. If blood pressure (BP) is \> 150 mm Hg (systolic) or \> 90 mm Hg (diastolic), the BP should be repeated two more times and the average of the three BP values should be used to determine the subject's eligibility. 12. Electrocardiographic (ECG) abnormalities of clinical significance as judged by the investigator. Screening supine 12-lead ECG demonstrating QTc \> 450 msec at Screening. 13. Any contraindications to obtaining a brain MRI (except for Part 4 subjects), DaT-SPECT (except for Part 4 subjects) or PET (e.g., claustrophobia unresponsive to reassurance or low dose of an anxiolytic agent, metal implants not compatible with MRI or known hypersensitivity to the active substance or to any of the excipients) and ability to tolerate lying in the scanner for up to \~180 minutes. 14. Previous exposure to radiation for medical, scientific or other reasons which could have a high negative impact on the research subject, as judged by the investigator. 15. Treatment with any other investigational therapy within 5 drug elimination half-lives or 30 days (whichever is longer) prior to inclusion in the study. Additional Exclusion Criteria for Healthy Volunteers: 16. Current use of CNS active drugs, including antidepressant or neuroleptic medications is not permitted, anti-inflammatory drugs or sleep medications may be allowed at the discretion of the investigator. 17. History of neurological disease/condition that may interfere with the objectives of the study, as judged by the investigator. Additional Exclusion Criteria for Participants with α-synucleinopathy: 18. Medical history indicating a Parkinsonian syndrome other than idiopathic PD, including but not limited to, progressive supranuclear palsy, drug-induced parkinsonism, essential tremor, vascular parkinsonism, primary dystonia or corticobasal syndrome (CBS). 19. Known carriers of certain familial PD gene mutations (PRKN, PINK1, DJ1, LRRK2), based on previous source documentation.