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There is a compelling need for a noninvasive imaging approach to measure S1P1 in both preclinical models of diseases and humans. PET measures of S1P1 expression is critical for elucidating the pathophysiological roles of S1P1 in neuroinflammation and neurodegeneration. The relevance of S1P1 in clinical disease has become readily apparent with the FDA approval of the S1P1 modulator FTY720 (fingolimod) for treating relapsing-remitting MS (RR-MS). MS is a chronic autoimmune, inflammatory disease caused by lymphocytic infiltration that leads to demyelinating neurodegenerative disease.
The primary objective of the initial IND study is to determine the safety of the [11C]-CS1P1 for PET imaging of S1P1 expression. The investigators will first complete whole-body PET dosimetry studies in healthy adult normal volunteers to calculate the actual radiation dose of each human organ and determine the allowable dose for a human subject when receiving a single dose for a PET scan. Second, complete imaging of the brain and lymph nodes of the neck in a wide range of ages of healthy adult normal control participants, both male and females to characterize [11C]-CS1P1 uptake in the brain and radiolabeled metabolite will be completed. Finally, a comparison of the normal control participants to patients with multiple sclerosis (MS) will be completed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental: [11C] CS1P1 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [11C]-CS1P1 | Drug | Participants will receive a single intravenous bolus injection of 6.0 - 20.0 mCi (222-740 MBq) of the investigational radiotracer [11C] CS1P1. Participants will then undergo a [11C] CS1P1 PET/CT scan. |
| Measure | Description | Time Frame |
|---|---|---|
| The tracer [11C]-CS1P1 will be injected for the first time into humans, using a dose range of 12-17 mCi for evaluations of safety, biodistribution, and dosimetry. | Whole-body PET/CT images (skull vertex to proximal thighs) will be obtained in 10 healthy volunteers (5 males and 5 females) for up to a maximum of 4 hours immediately following intravenous (IV) injection of 12-17 mCi of [11C]-CS1P1 (dosage range calculated from rodent dosimetry data extrapolated to humans). | 2 years |
| PET imaging studies of [11C]-CS1P1 in healthy normal control participants and human participants with multiple sclerosis. | We hypothesize that specific binding of [11C]-CS1P1 is elevated in participants with neuroinflammatory/neurodegenerative diseases of the CNS compared to healthy normal control participants. | 2 years |
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Inclusion Criteria:
Exclusion Criteria:
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Aim 1: Dosimetry/ Safety Group Ten healthy adult volunteers (5 males and 5 females) will be recruited and undergo whole-body PET/CT imaging for assessing the safety, dosimetry and metabolism of [11C]-CS1P1.
Aim 2: Feasibility Cohort Aim 2A will consist of 24 adult volunteers that will be recruited and scanned to characterize [11C] CS1P1 uptake on PET scans of the brain and cervical lymph nodes, to assess for radiolabeled metabolites. Up to 20 participants who have completed Aim 2A will continue with the collection of test-retest and safety data, Aim 2B. Ten healthy controls age and gender-matched to 10 participants with MS will be invited to return for repeat imaging for test-retest reliability not less than 7 days after and not more than 12 months after baseline imaging.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |