Leukocyte Tracking PET/MRI for Multiple Sclerosis

Overseen by Jonathan McConathy, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Alabama at Birmingham

Must not be taking: Antibiotics

Disqualifiers: Pregnancy, Cancer, Autoimmune, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study will use brain Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and an investigational radioactive drug called \[Zr-89\]oxine to track the location of white blood cells (also called leukocytes) in the body. PET/MRI will be used to visualize labeled white blood cells and determine if they enter the central nervous system in conditions associated with brain inflammation (also called neuroinflammation). By better understanding the role of neuroinflammation in fibromyalgia, chronic fatigue syndrome, and multiple sclerosis, the investigator hopes to be able to better diagnose and treat patients in the future.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment [Zr-89]Oxine-labeled leukocytes PET/MRI for tracking cells in multiple sclerosis?

Research shows that [Zr-89]Oxine is effective in tracking various immune cells using PET imaging, providing high-resolution and sensitive images. This method has been successfully used in preclinical studies to track cell migration and distribution, suggesting it could be useful for understanding cell behavior in diseases like multiple sclerosis. ^{1 2 3 4 5}

Is [Zr-89]Oxine-labeled leukocytes PET/MRI safe for humans?

Research shows that [Zr-89]Oxine-labeled leukocytes have been used in preclinical studies and have not compromised cell viability or function. The technique has been tested for safety in terms of cell labeling and imaging, with no significant negative effects observed in the studies. ^{1 2 3 4 5}

How does the treatment in the Leukocyte Tracking PET/MRI for Multiple Sclerosis trial differ from other treatments for this condition?

This treatment is unique because it uses a PET imaging technique with a radiotracer called 89Zr-oxine to track leukocytes (white blood cells) in the body, which helps monitor inflammation and immune cell movement in real-time. Unlike traditional treatments that focus on managing symptoms, this approach provides detailed insights into the disease process by visualizing cell migration, potentially leading to more personalized treatment strategies. ^{2 3 4 5 6}

Research Team

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for people aged 18-65 with fibromyalgia, chronic fatigue syndrome, multiple sclerosis, or healthy volunteers. It's not for those who are pregnant or lactating, have cancer, blood disorders, severe medical conditions preventing imaging procedures, recent serious infections, chronic infectious diseases like HIV/HCV or other autoimmune diseases (except MS).

Inclusion Criteria

I have been diagnosed with Chronic Fatigue Syndrome.

You are a person who is healthy and without any medical conditions.

I am between 18 and 65 years old.

Exclusion Criteria

You cannot have gadolinium-based contrast agents for medical reasons.

I do not have an autoimmune disease, except for MS.

I have a blood or clotting disorder.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive [Zr-89]oxine and undergo PET/MRI to track leukocyte infiltration in the brain

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• [Zr-89]Oxine-labeled leukocytes PET/MRI (Radiopharmaceutical)

Trial Overview [Zr-89]Oxine-labeled leukocytes PET/MRI is being tested to track white blood cells in the body and see if they move into the brain in patients with neuroinflammation-related conditions such as fibromyalgia and multiple sclerosis.

Participant Groups

Group I: Multiple Sclerosis Experimental Treatment 1 Intervention

Group II: Healthy Controls Experimental Treatment 1 Intervention

Group III: Fibromyalgia Experimental Treatment 1 Intervention

Group IV: Chronic Fatigue Syndrome Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Kierstin Kennedy

University of Alabama at Birmingham

Chief Medical Officer since 2022

MD

S. Dawn Bulgarella

University of Alabama at Birmingham

Chief Executive Officer since 2023

BSc in Commerce and Business Administration from the University of Alabama, MS in Health Administration from the University of Alabama at Birmingham

Findings from Research

Zirconium-89 (89Zr)-oxine ex vivo cell labeling for PET imaging allows for high-resolution tracking of anti-cancer T cell therapies in vivo for 1-2 weeks, demonstrating its potential for monitoring treatment effectiveness.

The low radioactivity doses used in 89Zr-oxine labeling do not interfere with the proliferation or function of immune cells, suggesting it is a safe method for imaging in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging of cell-based therapy using 89Zr-oxine ex vivo cell labeling for positron emission tomography. Kurebayashi, Y., Choyke, PL., Sato, N.[2021]

A new formulation of [89Zr]Zr-oxine was developed for radiolabelling white blood cells (WBCs), allowing for a quick and stable preparation process that could enhance cell tracking in patients.

While the labelling efficiency of [89Zr]Zr-oxine (48.7%) was lower than the current standard [111In]In-oxine (89.1%), both tracers showed similar cell viability and did not differ in terms of leukocyte chemotaxis or DNA damage, indicating that [89Zr]Zr-oxine is a promising alternative for PET imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A kit formulation for the preparation of [89Zr]Zr(oxinate)4 for PET cell tracking: White blood cell labelling and comparison with [111In]In(oxinate)3. Man, F., Khan, AA., Carrascal-Miniño, A., et al.[2022]

A novel labelling technique using the PET radioisotope zirconium-89 (89Zr) allows for efficient tracking of human leukocytes, achieving labelling efficiencies between 46% and 87% within 30-60 minutes.

The 89Zr-labelled leukocytes demonstrated stable in vivo behavior, with significant accumulation in the lung, liver, and spleen, making this method promising for monitoring immune responses and studying inflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-leukocyte labelling for cell trafficking: in vitro and preclinical investigations. Kahts, M., Guo, H., Kommidi, H., et al.[2023]

The production of the PET tracer [89 Zr]Oxinate4 for human use has been successfully developed, demonstrating high radiochemical purity and stability (>99%) at 24 hours post-synthesis, meeting all necessary quality control standards for clinical applications.

Importantly, [89 Zr]Oxinate4 does not compromise the viability of white blood cells and shows minimal cellular efflux within 3 hours post-labeling, indicating its potential for safe and effective imaging of cell trafficking in various diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production of [89 Zr]Oxinate4 and cell radiolabeling for human use. Massicano, AVF., Bartels, JL., Jeffers, CD., et al.[2022]

The 89Zr-oxine labeling method allows for effective tracking of natural killer (NK) cells in vivo using PET imaging, maintaining their viability and functionality when labeled at optimal radioactivity doses.

This technique enables visualization of NK cell migration and distribution for at least 7 days post-infusion, and it can also be applied to other cell types, enhancing its potential for various biomedical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tracking of NK Cells by Positron Emission Tomography Using 89Zr-Oxine Ex Vivo Cell Labeling. Sato, N., Szajek, LP., Choyke, PL.[2022]

The optimized procedure for isolating and radiolabeling leukocytes with 111In-oxine results in a 28% increase in labeling efficiency and maintains over 95% cell viability, making it a highly effective method for preparing leukocytes for imaging.

This method significantly reduces the time needed for preparation and eliminates contaminating red blood cells, ensuring a more accurate and efficient radiolabeling process for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation of 111In leukocytes after hemolytic removal of erythrocytes. Karesh, SM., Henkin, RE.[2019]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Imaging of cell-based therapy using 89Zr-oxine ex vivo cell labeling for positron emission tomography. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

A kit formulation for the preparation of [89Zr]Zr(oxinate)4 for PET cell tracking: White blood cell labelling and comparison with [111In]In(oxinate)3. [2022]

3. England pubmed.ncbi.nlm.nih.gov

89Zr-leukocyte labelling for cell trafficking: in vitro and preclinical investigations. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Production of [89 Zr]Oxinate4 and cell radiolabeling for human use. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Tracking of NK Cells by Positron Emission Tomography Using 89Zr-Oxine Ex Vivo Cell Labeling. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Preparation of 111In leukocytes after hemolytic removal of erythrocytes. [2019]