Application of 18F-CP6A PET Imaging in Synucleinopathies

NCT06827821 | Not Yet Recruiting Early Phase 1

• 1 other identifier: XLan-1220
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Synucleinopathies

Outcome Measures

Primary Outcomes (1)

• 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.

  From enrollment to the end of imaging at 4 weeks

Secondary Outcomes (2)

• Radioactivity in the blood and urine samples

  From enrollment to the end of imaging at 4 weeks

• Radiation doses in healthy subjects

  From enrollment to the end of imaging at 4 weeks

Study Arms (1)

PET imaging targeting α-synuclein in synucleinopathies

EXPERIMENTAL

Determine if targeting α-synuclein PET is safe and effective method for imaging of synucleinopathies

Drug: 18F-CP6A

Interventions

18F-CP6A DRUG

For 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.

PET imaging targeting α-synuclein in synucleinopathies

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Volunteers:
• Fully understand and voluntarily sign the informed consent form.
• 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.
• No history of other neurological or chronic diseases in the last 3 years.
• No abnormal vital signs or physical examination findings.
• No pregnancy or lactation, and willing to use effective contraception during the trial period and for 6 months post-study.
• No participation in other clinical trials within the past month.
• Able to communicate effectively with the study team and understand and comply with the study requirements.
• Synucleinopathy Patients:
• Ability to sign the informed consent form or by a legal representative.
• Aged 50-80 years, any gender.
• Clinically diagnosed or suspected PD, MSA, or DLB based on diagnostic criteria \[including China's Parkinson's Disease Diagnosis (2016), MSA Consensus (2022), and DLB Guidelines (2021)\].
• No other neurological diseases, severe chronic diseases, or malignancies.

You may not qualify if:

• Healthy Volunteers:
• 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.
• Inability to undergo PET/MRI or PET/CT imaging (e.g., claustrophobia).
• Participation in studies involving radioactive substances within the last 12 months.
• Any other factor that may interfere with study results.
• Synucleinopathy Patients:
• Inability or unwillingness to sign the informed consent form.
• Pregnant or breastfeeding participants.
• History of other neurological diseases or severe chronic illnesses.
• Known allergy to α-Syn imaging agents or synthetic excipients.
• Inability to complete PET/MR or PET/CT imaging.
• Researcher assesses poor compliance or other conditions that would render participation unsuitable.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Shenzhen Braegen Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

MeSH Terms

Conditions

Synucleinopathies

Condition Hierarchy (Ancestors)

Neurodegenerative Diseases; Nervous System Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Xiaoli Lan, PhD

CONTACT

0086-027-83692633; lxl730724@hotmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2024
• First Posted: February 14, 2025
• Study Start: February 17, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 14, 2025

Record last verified: 2025-02

Locations

CN (1)