TSPO-PET/MRI in Surveillance of Neuroinflammation in the Central Nervous System

An Oberservational Study of Utility of TSPO-PET/MRI Using the Radiotracer ([18F]-DPA-714) in Surveillance of Neuroinflammation in the Central Nervous System

Central Nervous System (CNS) inflammation is an immune response activated in the brain and spinal cord by microglial cells and astrocytes, commonly occurring under conditions such as central nervous system ischemia, autoimmunity, infection, toxins, and trauma.

Microglial cells, as the innate immune cells of the central nervous system, are responsible for driving the inflammatory response and play a crucial role in sensing environmental changes, responding to harmful stimuli, and engulfing dead neurons. They also present antigens to T lymphocytes, mediating interactions between the peripheral immune system and the central nervous system. Factors released by neuronal cells can either promote or inhibit inflammation, and monitoring the level of inflammation driven by microglial cells is essential for the diagnosis and treatment of central nervous system diseases.

MRI is the primary imaging method for central nervous system inflammation, but it can be challenging to diagnose. PET/MR, a technology that integrates PET and MR imaging, provides high-quality diagnostic images and is valuable for the early detection, diagnosis, and assessment of central nervous system diseases. The radioactive ligand 18F-DPA-714 PET, targeting the translocation protein (TSPO), can visualize activated microglial cells, which may have a gain effect in detecting active central nervous system inflammation.

This study aims to explore the application of 18F-DPA-714 PET/MR in the early diagnosis, treatment evaluation, and prognosis of central nervous system inflammation.

Study Overview

• Status: Recruiting
• Conditions: Central Nervous System Diseases
• Intervention / Treatment: Radiation: Radiation: PET-MRI with [18F]-DPA-714

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Luo-qi Zhou, MD; Phone Number: 86-27-83663337; Email: zhouluoqi@tjh.tjmu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
      • Principal Investigator: Wei Wang, MD
      • Sub-Investigator: Chuan Qin, MD
      • Sub-Investigator: Jun Xiao, MD
      • Contact: Luo-qi Zhou, MD; Phone Number: 86-27-83663337; Email: zhouluoqi@tjh.tjmu.edu.cn
      • Sub-Investigator: Dai-shi Tian, MD
      • Sub-Investigator: Xiao-hua Zhu, MD
      • Sub-Investigator: Si-yuan Cheng, MD
      • Sub-Investigator: Luo-qi Zhou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosis with central nervous system diseases (lesions occurring in the brain or spinal cord, such as stroke, autoimmune encephalitis, neuromyelitis optica spectrum disorders, multiple sclerosis, etc.)

Description

Inclusion Criteria:

-Clinical diagnosis of ischemic stroke, autoimmune ecephalitis, Neuromyelitis optica spectrum disorders, or multiple sclerosis, etc.al

Exclusion Criteria:

• Claustrophobia
• Metal Implants
• Pregancy
• Breast-feeding
• Renal insufficiency (GFR < 60 mL/min/1.73m2)
• Allergy or other contraindication to gadolinium-based MR contrast agent

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ICVD; ischemic cerebrovascular diseases	Radiation: Radiation: PET-MRI with [18F]-DPA-714; Radiation: PET-MRI with [18F]-DPA-714
Neurological Autoimmune Diseases; Multiple Sclerosis，Neuromyelitis Optica Spectrum Disorders and Autoimmune Encephalitis	Radiation: Radiation: PET-MRI with [18F]-DPA-714; Radiation: PET-MRI with [18F]-DPA-714
other; other encephalomyelitis	Radiation: Radiation: PET-MRI with [18F]-DPA-714; Radiation: PET-MRI with [18F]-DPA-714

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in TSPO Radiotracer Uptake	Quantify the regional neuroinflammatory load, measured as binding of PET tracer to TSPO.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free Diffusing Water Fraction	Calculated using MR-DWI	12 months
Peripheral Levels of Pro-Inflammatory Cytokines	Evaluated using blood samples, including IL-6, IL-4, IL-10, hs-CRP and PCT etc,al	12 months
MRI Correlation	Correlation of white matter lesion volume and MRI measures of white matter tract injury determined from DTI with measures of TSPO uptake	12 months
CSF Levels of Pro-Inflammatory Cytokines	Evaluated using cerebrospinal fluid, IL-6, IL-4, IL-10, hs-CRP and PCT etc, al	12 months
CSF Levels of neural injury markers	Evaluated using cerebrospinal fluid, GFAP, NFL and sTREM2 etc, al	12 months
Inflammatory Markers correlation	Correlation of PET derived measures of TSPO uptake with inflammatory markers (IL-6, IL-4, IL-10, hs-CRP and PCT etc, al) in the blood or cerebrospinal fluid	12 months
Neural injury markers correlation	Correlation of PET derived measures of TSPO uptake with neural injury markers ( GFAP, NFL and sTREM2) in the cerebrospinal fluid	12 months

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Collaborators: Wuhan Jianmin DAPENG Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Wei Wang, MD, Tongji Hospital

Publications and helpful links

General Publications

• Shi K, Tian DC, Li ZG, Ducruet AF, Lawton MT, Shi FD. Global brain inflammation in stroke. Lancet Neurol. 2019 Nov;18(11):1058-1066. doi: 10.1016/S1474-4422(19)30078-X. Epub 2019 Jul 8.
• Kwon HS, Koh SH. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl Neurodegener. 2020 Nov 26;9(1):42. doi: 10.1186/s40035-020-00221-2.
• Voet S, Prinz M, van Loo G. Microglia in Central Nervous System Inflammation and Multiple Sclerosis Pathology. Trends Mol Med. 2019 Feb;25(2):112-123. doi: 10.1016/j.molmed.2018.11.005. Epub 2018 Dec 18.
• Kreisl WC, Kim MJ, Coughlin JM, Henter ID, Owen DR, Innis RB. PET imaging of neuroinflammation in neurological disorders. Lancet Neurol. 2020 Nov;19(11):940-950. doi: 10.1016/S1474-4422(20)30346-X.
• Zhang M, Meng H, Zhou Q, Chunyu H, He L, Meng H, Wang H, Wang Y, Sun C, Xi Y, Hai W, Huang Q, Li B, Chen S. Microglial Activation Imaging Using 18F-DPA-714 PET/MRI for Detecting Autoimmune Encephalitis. Radiology. 2024 Mar;310(3):e230397. doi: 10.1148/radiol.230397.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: June 12, 2024
• First Submitted That Met QC Criteria: June 20, 2024
• First Posted (Actual): June 21, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2025
• Last Update Submitted That Met QC Criteria: April 6, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Neuroinflammatory Diseases; Nervous System Diseases; Central Nervous System Diseases
• Other Study ID Numbers: PETinCNS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No