Background:
Multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML) are disorders that affect the central nervous system (CNS). The CNS includes the brain, spinal cord, and optic nerves. Both diseases can cause muscle weakness and impair vision, speech, and coordination. Researchers are working to better understand how MS and PML affect the CNS.
Objective: To test whether an experimental radioactive tracer (minibody) can help positron emission tomography (PET) scans detect certain immune cells in the CNS of people with MS and PML.
Eligibility:
People aged 18 years and older with MS, other neuroinflammatory diseases with BBB leakage, or PML.
Design:
Participants will come to the clinic for at least 3 visits over 4 to 6 weeks.
Participants will undergo testing. They will have a physical and neurological exam. They will have blood tests and tests of their heart function. They will have a magnetic resonance imaging (MRI) scan of the brain. They may have a spinal tap: Their lower back will be numbed, and a needle will be inserted between the bones of the spine to withdraw fluid from around the spinal cord.
Minibody is given through a tube with a needle placed in a vein in the arm. This takes 5 to 10 minutes. Participants will have heart function tests before and after receiving the minibody.
Participants may have a PET scan on the day of the Minibody and will return the next day for another PET scan. They will lie on a table that moves through a doughnut-shaped machine. This scan will take about 1 hour.
Participants with PML may opt to repeat the minibody infusion and the PET scan within 6 months.
Enrolled in the NINDS Natural History Study for MS (protocol 89-N-0045)
Able to understand, and willing to sign, a written, informed consent document.
Willing to comply with all study procedures and available for the duration of the study.
Male or female, aged >=18.
Pregnant or lactating.
Contraindications for MRI gadolinium contrast administration or 3T MRI.
History of, or current diagnosis with, concomitant medical or clinical conditions that would adversely affect participation in this study.
Weighs > 350 lb. (158 kg; weight limit for the scanner table) or is unable to fit within the MRI or PET imaging gantry.
Single group
89 Zr-Df-crefmirlimab
Drugan 80 kDa minibody (Mb) with high affinity to CD8 glycoprotein (binding EC50 = 0.4 nM) that is conjugated with deferoxamine (Df) and radiolabeled with the positron emitting radionuclide, Zr-89 (T1/2 78.4 hours).
Infiltration of CD8+ T cells in the CNS of adults with MS and PML via PET-CT scans using a minibody with high affinity for CD8+ T cells.
To detect and localize infiltration of CD8+ T cells in the CNS of adults with MS and PML via PET-CT scans using a minibody with high affinity for CD8+ T cells.
For the PML cohort with longitudinal evaluation, effects of immune reconstitution, either spontaneous or facilitated, on 89Zr-Dfcrefmirlimab uptake.
Comparison of SUV before and after immune reconstitution, either spontaneous or facilitated (for participants with optional follow-up imaging).
Safety of 89Zr-Dfcrefmirlimab in the participants with CNS disease.
To assess the safety of 89Zr-Dfcrefmirlimab in participants with CNS disease.
To determine whether 89Zr-Df-crefmirlimab uptake profile in MS and PML is disease-specific.
Understand the physiological pattern of 89Zr-Df-crefmirlimab distribution corresponding to normal accumulation of CD8+ T cells.
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