Evaluation of a Novel PET Radioligand to Image Cyclooxygenase-1 (COX-1)
Condition: Normal Physiology
Study type: Observational

Summary: 
      Background:

      A radioligand is a radioactive substance that is used to diagnose diseases. A new ligand is
      called [11C]PS13. This has a small amount of radioactivity that can be detected by a positron
      emission tomography (PET) scan. If this ligand works well in this study, researchers may be
      able to use it to better understand and diagnose brain disorders.

      Objectives:

      To evaluate if [11C]PS13 can measure its receptor, which is involved in inflammation. To see
      if researchers get the same results when scanning a person twice.

      Eligibility:

      Healthy people ages 18 and older who are in Protocol 01-M-0254.

      Design:

      This study requires three visits of 2-5 hours each.

      Participants will have 2 PET scans with [11C]PS13.

      A needle will guide a small plastic tube (catheter) into an arm vein. The needle will be
      removed, leaving only the catheter in the vein. The ligand will be injected through the
      catheter.

      The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and
      out of the scanner.

      Participants will wear a molded a plastic mask that fits the head.

      Another catheter will be put into an artery at the wrist or elbow area.

      Vital signs will be monitored during the PET scan. Participants will have a test during the
      PET scan to monitor heart function.

      Participants will have blood and urine tests.

      Participants will have 1 magnetic resonance imaging (MRI) scan. The MRI scanner is a metal
      cylinder surrounded by a strong magnetic field. Participants will lie on a table that slides
      in and out of the cylinder.

      ...
    

Detailed description: 
      Objective

      The cyclooxygenase (COX) system is implicated in the pathophysiology of brain diseases,
      including Alzheimer s disease and depression, and is a potential biomarker for
      neuroinflammation. COX is the rate-limiting enzyme in the synthesis of prostaglandins from
      arachidonic acid and exists as two primary isoforms COX-1 and COX-2. Our laboratory recently
      developed [(11)C]PS13, a novel PET ligand to selectively image COX-1, and initial PET scans
      in monkey demonstrated that [11C]PS13 is a promising ligand.

      This study has two primary objectives. First, we will determine whether the uptake of
      [(11)C]PS13 in brain and periphery reflects the distribution of COX-1, as demonstrated by
      blocking with a COX-1 preferential drug (aspirin or ketoprofen) and/or no effect with a COX-2
      selective drug (celecoxib). Second, we will measure the test/retest reproducibility of brain
      uptake quantified by compartmental modeling and using arterial and/or venous blood samples.

      Study Population

      Healthy adult volunteers (aged 18 years or older) will have either whole body imaging (n =
      41) or brain imaging (n = 20).

      Design

      Phase 1: We will begin with whole body scanning in a single human subject using up to 10 mCi.
      The aim of this first scan will be to detect a tracer that disproportionately accumulates in
      a single radiosensitive organ, such as the gonads. If we confirm that radioactivity is fairly
      widely distributed in the body, higher activities may be injected.

      Phase 2:Thirty healthy subjects will have three whole body imaging PET scans using 20 mCi of
      [11C]PS13. Scan 1 will serve as the baseline scan for comparison to enzyme occupancy studies
      and will provide dosimetry information. Scan 2 will be an enzyme occupancy study using the
      COX-2 selective antagonist celecoxib. Scan 3 will be an enzyme occupancy study using the
      COX-1 preferential antagonist aspirin. Ten healthy subjects will have two whole body imaging
      PET scans using 20 mCi of [11C]PS13. Scan

      1 will serve as the baseline scan, and scan 2 will be an enzyme occupancy study using another
      potent COX-1 antagonist ketoprofen.

      Phase 3: We will perform 15 test retest kinetic brain imaging PET studies with arterial
      and/or venous blood sampling and 5 test retest brain PET studies with both arterial and
      venous blood sampling, using a 20 mCi dose of [(11)C]PS13.

      Outcome Measures

      For whole body imaging, organ uptake will be quantified as a Standardized Uptake Value (SUV),
      which normalizes for injected activity and body weight. Blockade by aspirin, ketoprofen, and
      celecoxib will be expressed as a percentage of the baseline scan in each subject and plotted
      relative to the plasma concentration of the drug at time of the PET scan. For dedicated brain
      imaging, uptake will be quantified as distribution volume (VT) calculated with compartmental
      modeling and serial concentrations of parent radioligand in arterial and/or

      venous plasma.
    

Intervention name(s): [11C]PS13
Intervention type(s): Drug
Intervention description(s): A novel PET ligand to selectively image COX-1
Observational model: Cohort
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        Community sample
      
Keywords: Research; Brain; Inflammation; Natural History