Synucleinopathies are a group of severe neurodegenerative diseases, including Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy (MSA). A common feature of these diseases is the pathological aggregation of α-synuclein (α-Syn), which forms Lewy Bodies (LBs), directly causing neuronal damage and death. Clinically, these diseases can present similar parkinsonian syndromes, making differential diagnosis more challenging. However, they may exhibit significant differences in the distribution and morphology of α-Syn pathology. For example, in MSA, the pathological α-Syn primarily accumulates in oligodendrocytes, particularly in the brainstem and cerebellar white matter, which differs significantly from the neuronal Lewy Body formation seen in PD and DLB.
Currently, imaging biomarkers related to β-amyloid (Aβ) and tau proteins have been widely used in clinical diagnosis and research. However, imaging biomarkers targeting α-Syn are still relatively lacking, which limits the early diagnosis and accurate subtyping of these diseases.
In recent years, some PET imaging agents targeting α-Syn have demonstrated good affinity in vitro and in animal experiments, significantly outperforming other common neurodegenerative biomarkers, including Aβ and tau proteins. These agents show promising potential in aiding the diagnosis of synucleinopathies. Professor Ye Keqiang's team at Shenzhen University of Technology has previously developed a small molecule compound (F0502B) with high affinity and selectivity for α-Syn aggregates. Early in vivo and in vitro experiments showed that it could specifically bind to LBs and quantify the amount of LBs in the brain, aiding the early detection of preclinical PD patients and dynamic monitoring of disease progression. Further optimization of the F0502B compound led to the development of its derivative, CP6A. The 18F-labeled probe of CP6A preferentially highlights α-Syn deposition in the brains of animal models and has demonstrated good safety in both mice and monkeys.
Based on the above, this project intends to include clinically diagnosed or highly probable synucleinopathy patients and healthy volunteers, using the 18F-labeled derivative of the α-synuclein-specific imaging agent, 18F-CP6A, to perform integrated PET imaging. The goal is to explore the in vivo safety, pharmacokinetics, and clinical application value of 18F-CP6A in synucleinopathies.
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Aged 18-65 years, any gender.
Male weight ≥ 50.0 kg, female weight ≥ 45.0 kg; BMI within 19.0-26.0 kg/m2.
Non-synucleinopathy, normal motor function, UPDRS score of 0.
Any severe or unstable medical condition, acute diseases prior to the study.
Pregnant or breastfeeding women.
Any surgery within the last 6 months that could affect drug absorption, distribution, metabolism, or excretion.
Use of any medication (prescription or over-the-counter) within 2 weeks prior to the study.
Single group
18F-CP6A
DrugFor pharmacokinetics, healthy volunteers underwent PET imaging targeting α-synuclein. Blood samples were collected at before and 2 ± 1, 5 ± 2, 10 ± 2, 30 ± 5, 60 ± 5, 90 ± 5, and 120 ± 10 min after imaging agent injection, and urine specimens were collected at before and 0-1.5, and 1.5-3 h after injection to measure radioactivity in blood and urine. PET/MR and PET/CT scans were performed at 0 ± 10, 30 ± 10, 60 ± 10, and 100 ± 10 min after injection to understand distribution for healthy volunteers and synucleinopathy patients. A separate 10-minute PET scan of the brain is required of each acquisition. Blood tests, liver and kidney function, and other biochemical markers must be performed one week prior to and after imaging.
Visual and standardized uptake values assessment of biodistribution
At least two experienced nuclear medicine physicians will conduct a visual analysis using consensus reading. The standardized uptake value (SUV) of brain and other organs will be measured after a semiquantitative analysis is conducted for each case. The SUV ranges from 0 to infinity, and a higher score means a higher uptake of targeting α-synuclein probe by the tumor, which implies a greater possibility of synucleinopathies.
Radioactivity in the blood and urine samples
Blood samples will be collected at before injection of 18F-CP6A, and 2 ± 1、5 ± 2、10 ± 2、30 ± 5、60 ± 5、90 ± 5、120 ± 10 minutes after injection. Urine samples were collected at before injection of 18F-CP6A, and 0-1.5 and 1.5-3 hours after injection. Radioactivity in the blood and urine samples will be measured by gamma counters.
Radiation doses in healthy subjects
Calculate the radiation equivalent dose (in mSv/MBq) to each organ tissue in healthy subjects, including: brain, heart, liver, spleen, lungs and kidneys, using OLINDA/EXM software.
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Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Lead sponsor
Shenzhen Braegen Pharmaceutical Co., Ltd.
Collaborator
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