Phase 1 Study to Evaluate [18F]ACI-15916 as a Potential PET Radioligand for Imaging α-synuclein Deposits in the Brain of Patients With Suspected α-synuclein Pathology Compared With Healthy Volunteers
The goal of this clinical trial is to test whether we can reliably and safely measure the accumulation of pathological protein α-synuclein \[involved in some diseases such as Parkinson's disease, Lewy body dementia and Multiple System Atrophy (MSA), collectively named α-synucleinopathies\] using a new positron emission tomography (PET) tracer called \[18F\]ACI-15916. Both healthy people and people with (suspected) α-synuclein pathology will participate to this trial. The main questions it aims to answer are: * whether \[18F\]ACI-15916 is safe and well tolerated when injected into participants * whether \[18F\]ACI-15916 reliably detects α-synuclein in the brain using PET technique. * whether there are differences in the amount of this protein between people with diseases related to α-synuclein accumulation in the brain and people without these diseases. Participants will: * Visit the clinic to consent to their participation and to ensure they are eligible \[physical and neurological examinations, questionnaires, blood and urine tests, ECG and in some cases a MRI and a PET scan with a licensed tracer (\[18F\]FE-PE2I) to confirm or not the disease\]. * Visit the clinic to receive the tracer \[18F\]ACI-15916 intravenously and be scanned in a PET scanner, during which blood will be collected (and optionally spinal fluid). * Receive a phone call from the clinic 1 week after the PET scan to report any symptoms and side-effects that they may be having. Some of the participants may be asked to come again to the clinic for a second PET scan with \[18F\]ACI-15916, allowing the researchers to determine if the measurements with the first PET scan are stable and reproducible. Some of the participants will participate in a specific part of the study to evaluate the distribution of the PET ligand in the whole body, with a similar visit schedule.
• Subject is able to provide written informed consent, which must be obtained before any assessment is performed.
• Subjects must be able to understand and be willing to comply with study procedures, restrictions, and requirements.
• Body mass index is \> 18 and \< 31 kg/m2 and Bodyweight ≥ 50 kg and ≤ 100 kg.
• Female participants must not be of childbearing potential or agree to use highly effective methods of contraception.
• 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:
• Males and females aged ≥ 20 at the time of signing the informed consent.
• Normal MRI and DAT PET or SPECT (except for Part 4 participants), as judged by the investigator.
• 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.
• No family history of α-synucleinopathy, including PD, or other early-onset neurological disease associated with dementia.
⁃ No personal history of clinically significant neurologic and/or psychiatric disorders.
⁃ Have a Montreal Cognitive Assessment (MoCA) score ≥ 26
⁃ No cognitive impairment as judged by the PI or delegated physician.
⁃ Additional Inclusion Criteria for Participants with α-synucleinopathies:
⁃ Males and females aged ≥ 40 at the time of signing the informed consent.
⁃ 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)
⁃ 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.
⁃ 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.