Investigation of Inflammation Using [C-11]-CS1P1

Study Overview
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Brief Summary
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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.

Official Title
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Investigation of Inflammation Using [C-11]-CS1P1

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: [11C]-CS1P1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, any race; Age ≥ 18 years; Capable of providing written informed consent for volunteering to undergo research procedures. Healthy volunteer or volunteer with a diagnosis of MS Exclusion Criteria: Hypersensitivity to [11C]-CS1P1 or any of its excipients; Contraindications to PET, CT or MRI (e.g. certain incompatible electronic medical devices, inability to lie still for extended periods) that make it potentially unsafe for the individual to participate; Severe claustrophobia Women who are currently pregnant or breast-feeding; Currently undergoing radiation therapy; Any condition that, in the opinion of the Sponsor-Investigator or designee could increase risk to the participant, limit the participant's ability to tolerate the research procedures or interfere with collection of the data (e.g., renal or liver failure, advanced cancer); Participants who in the last 6 months experienced any of the following cardiovascular conditions or findings in the screening electrocardiogram (ECG): unstable cardiac arrhythmias, myocardial infarction, unstable angina, stroke, transient ischemic attack or decompensated heart failure requiring hospitalization or Class III/IV heart failure; Must not have participated in any clinical trial involving a study drug or device within the 30-days prior to study enrollment; Must not participate in another drug or device study prior to the end of this study participation; Current or recent (within 12 months prior to screening) participation in research studies involving radioactive agents such that the total research-related radiation dose to the participant in any given year would exceed the limits set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.1.

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [11C] CS1P1<br> | Drug: [11C]-CS1P1<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 |