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

• [Zr-89]Oxine-labeled leukocytes PET/MRI (Drug): 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.

Primary outcomes

• Regional brain distribution of radiolabeled white blood cells [3 years]: 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.

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

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:

1. Contraindication to MRI
2. Pregnancy
3. Lactation
4. Individuals who are unable to participate in the imaging portion due to severity of their medical condition
5. Chronic infectious disease (e.g. HIV, HCV)
6. Viral or bacterial illness requiring medical attention and/or antibiotics within 1 month of study participation
7. Diagnosis of cancer, including leukemia
8. Blood or blood clotting disorder
9. Except for individuals with MS, a diagnosis of autoimmune disease is exclusionary
10. 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
11. Currently enrolled in a clinical trial utilizing experimental therapies
12. Contraindication to gadolinium based contrast agents

• Results publication: Gultekin K, Bartels JL, Cardenas CE, Kumar Y, Gimblet GR, Jones CL, Bankston C, Jeffers CD, White SL, Lapi SE, Younger JW, McConathy JE. First-in-human dosimetry and biodistribution of [89Zr]Zr-oxine-labeled autologous leukocytes using PET/CT. Eur J Nucl Med Mol Imaging. 2026 Oct 2. doi: 10.1007/s00259-026-08158-w. Online ahead of print. PMID 42825819

• Jonathan McConathy, MD,PhD, Principal investigator, University of Alabama at Birmingham