Leukocyte Tracking PET/MRI for Multiple Sclerosis

Overseen By Jonathan McConathy, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Antibiotics

Disqualifiers: Pregnancy, Cancer, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand brain inflammation in conditions like multiple sclerosis, fibromyalgia, and chronic fatigue syndrome. Researchers use a special imaging technique called PET/MRI to track the movement of white blood cells labeled with a radioactive drug ([Zr-89]Oxine-labeled leukocytes). By observing these cells, they hope to improve diagnosis and treatment options for these conditions. The trial seeks participants diagnosed with multiple sclerosis, fibromyalgia, or chronic fatigue syndrome. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking insights.

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 prior data suggests that this PET/MRI technique is safe for tracking leukocytes?

In a previous study, researchers used a substance called [Zr-89]oxine to label and track white blood cells in the body. The results showed that this method did not harm the cells' ability to survive, grow, or function, suggesting that the treatment might be safe. However, as this is an early-stage study, limited information exists about its safety. Participants in this trial will help researchers learn more about the safety and possible side effects of using [Zr-89]oxine in people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Leukocyte Tracking PET/MRI trial for multiple sclerosis because it offers a fresh way to understand disease activity. Unlike standard treatments, which typically focus on managing symptoms or slowing disease progression, this method uses [Zr-89]Oxine-labeled leukocytes in combination with PET/MRI to visualize immune system activity directly within the brain. This innovative approach provides a unique window into how immune cells behave, potentially leading to breakthroughs in how multiple sclerosis is diagnosed and monitored. By gaining clearer insights into the disease mechanisms, it could pave the way for more effective treatment strategies in the future.

What evidence suggests that this PET/MRI technique is effective for tracking leukocytes in neuroinflammation?

Research has shown that [Zr-89]oxine can label white blood cells, enabling doctors to track them in the body using PET/MRI scans. This method shows promise for detecting infections by visualizing the movement of white blood cells. In earlier studies, labeling with [Zr-89]oxine did not harm the cells or alter their function, ensuring accurate imaging. The process efficiently labels a high number of white blood cells for tracking. This trial will employ this technique to study immune cell movement into the brain, potentially enhancing understanding of conditions like multiple sclerosis, fibromyalgia, and chronic fatigue syndrome. ^{1 2 3 4 5}

Who Is on the Research Team?

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

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.

You have been diagnosed with fibromyalgia based on specific guidelines from the American College of Rheumatology.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4456181/

89Zr-Oxine Complex PET Cell Imaging in Monitoring ... 89Zr-oxine complex cell labeling enables highly sensitive in vivo cell tracking with PET without interfering with cell survival, proliferation, or function.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11440985/

First-in-human infection imaging with 89Zr-labelled ... Our first-in-human study utilising the cell surface labelling approach aimed to image infection in patients with the use of 89 Zr-labelled leukocytes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03807973?intr=OXYQUINOLINE&aggFilters=studyType:int&viewType=Table&rank=3

Tracking Peripheral Immune Cell Infiltration of the Brain in ... This study will use brain Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and an investigational radioactive drug called [Zr-89]oxine to ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0969805120301827

A kit formulation for the preparation of [89Zr]Zr(oxinate)4 ... This study demonstrates a 1-step procedure for preparing [ 89 Zr]Zr-oxine and evaluates it against [ 111 In]In-oxine in white blood cell (WBC) labelling.

5. ejnmmipharmchem.springeropen.com ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-023-00223-1

89Zr-leukocyte labelling for cell trafficking: in vitro and ... The 89Zr-leukocyte labelling efficiency ranged from 46 to 87% after 30–60 min. Radioactivity concentrations of labelled cells were up to 0.28 ...