Tracking Peripheral Immune Cell Infiltration of the Brain in Central Inflammatory Disorders Using [Zr-89]Oxinate-4-labeled Leukocytes.

Study Overview
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Brief Summary
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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.

Official Title
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Tracking Peripheral Immune Cell Infiltration of the Brain in Central Inflammatory Disorders Using [Zr-89]Oxinate-4-labeled Leukocytes.

Conditions
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Fibromyalgia, Chronic Fatigue Syndrome, Multiple Sclerosis, Healthy

Intervention / Treatment
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* Drug: [Zr-89]Oxine-labeled leukocytes PET/MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.18 to 65 years of age 2.Healthy volunteer OR Clinical diagnosis of Multiple Sclerosis (MS) OR Meets 2016 American College of Rheumatology (ACR) case definition criteria for fibromyalgia OR Meets 1994 Fukuda case definition criteria for Chronic Fatigue Syndrome Exclusion Criteria: Contraindication to MRI Pregnancy Lactation Individuals who are unable to participate in the imaging portion due to severity of their medical condition Chronic infectious disease (e.g. HIV, HCV) Viral or bacterial illness requiring medical attention and/or antibiotics within 1 month of study participation Diagnosis of cancer, including leukemia Blood or blood clotting disorder Except for individuals with MS, a diagnosis of autoimmune disease is exclusionary Positive urine pregnancy test day of procedure or a serum pregnancy test within 48 hours prior to the administration of Zirconium-89 Oxinate-4-labeled leukocytes Currently enrolled in a clinical trial utilizing experimental therapies Contraindication to gadolinium based contrast agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fibromyalgia<br> | Drug: [Zr-89]Oxine-labeled leukocytes PET/MRI<br>* All study participants will undergo an investigational imaging study using autologous [Zr-89]-labeled leukocytes and brain PET/MRI. Participants will undergo a venous blood draw, and the leukocytes in the blood sample will be isolated for labeling using [Zr-89]oxine. The labeled leukocytes (7.4- 18.5 megabecquerel (MBq), 200-500 uCi) will be re-injected into the participant followed by brain PET/MRI at 24-48 hours after injection. Participants will be asked to have a second brain imaging study 3-6 days after this injection, but this second imaging study is optional.<br>|
| Experimental: Chronic Fatigue Syndrome<br> | Drug: [Zr-89]Oxine-labeled leukocytes PET/MRI<br>* All study participants will undergo an investigational imaging study using autologous [Zr-89]-labeled leukocytes and brain PET/MRI. Participants will undergo a venous blood draw, and the leukocytes in the blood sample will be isolated for labeling using [Zr-89]oxine. The labeled leukocytes (7.4- 18.5 megabecquerel (MBq), 200-500 uCi) will be re-injected into the participant followed by brain PET/MRI at 24-48 hours after injection. Participants will be asked to have a second brain imaging study 3-6 days after this injection, but this second imaging study is optional.<br>|
| Experimental: Multiple Sclerosis<br> | Drug: [Zr-89]Oxine-labeled leukocytes PET/MRI<br>* All study participants will undergo an investigational imaging study using autologous [Zr-89]-labeled leukocytes and brain PET/MRI. Participants will undergo a venous blood draw, and the leukocytes in the blood sample will be isolated for labeling using [Zr-89]oxine. The labeled leukocytes (7.4- 18.5 megabecquerel (MBq), 200-500 uCi) will be re-injected into the participant followed by brain PET/MRI at 24-48 hours after injection. Participants will be asked to have a second brain imaging study 3-6 days after this injection, but this second imaging study is optional.<br>|
| Experimental: Healthy Controls<br> | Drug: [Zr-89]Oxine-labeled leukocytes PET/MRI<br>* All study participants will undergo an investigational imaging study using autologous [Zr-89]-labeled leukocytes and brain PET/MRI. Participants will undergo a venous blood draw, and the leukocytes in the blood sample will be isolated for labeling using [Zr-89]oxine. The labeled leukocytes (7.4- 18.5 megabecquerel (MBq), 200-500 uCi) will be re-injected into the participant followed by brain PET/MRI at 24-48 hours after injection. Participants will be asked to have a second brain imaging study 3-6 days after this injection, but this second imaging study is optional.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional brain distribution of radiolabeled white blood cells | Descriptive statistics (means and standard deviations) of standardized uptake values (SUVs) will be presented for the patient groups and healthy controls in the following regions: whole brain, gray matter, white matter, atlas-based regions of interest, and lesions (MS patients only). Normality of the SUV distribution will be tested using Shapiro-Wilk tests, and the data will be transformed to normal distribution if necessary. | 3 years |