PET/CT of Skeletal Muscle Amino Acid Kinetics
Condition: Sarcopenia
MeSH terms: Sarcopenia
Study type: Observational

Summary: 
      Our goal is to develop and test a new imaging technique to help scientists study sarcopenia,
      the process by which muscle becomes weaker with age. This imaging technique uses Positron
      Emission Tomography/Computed Tomography (PET/CT) scanners to measure the ability of muscle to
      synthesize new protein. This ability to build new muscle protein is known as the Protein
      Synthesis Rate, and is thought to decline as people age and to contribute to muscle
      weakening. We are researching this technique in order to develop a tool to help scientists
      and physicians better understand how muscle ages and how it changes based on some stimulus,
      such as when people eat a high protein meal, exercise, or take muscle-building drugs. If our
      research is successful, it will provide a new method for scientists and physicians to test
      the effectiveness of new drugs and other treatments for muscle weakness. The study will look
      for healthy woman between the ages of 65 and 80.
    

Detailed description: 
      On 2 separate visits, with approximately 2 weeks in between visits. For each visit the
      volunteer will be required to fast overnight (no food or drink for 10 hours prior to arrival
      at UCSF (water is OK)).

      Visit 1 will last approximately 5-6 hours. Visit 2 will last approximately 8 hours. Each
      visit will include the same general procedures, with the second visit varying slightly from
      the first (described below). Including the 10-hour overnight fast, both visits will entail
      roughly 15 hours of continuous fasting. After completion of Visit 1, snacks and drinks will
      be available. For Visit 2, the volunteer will have a protein drink roughly 4-5 hours into the
      visit, and snacks and drinks will be made available when the visit is over.

      After checking in, the volunteer will be admitted to the Imaging Suite. i) Catheters At the
      beginning of each visit, a nurse will place two flexible plastic catheters in veins in the
      forearms. The catheters will be used to collect blood samples to measure changes in hormone
      and amino acid levels. They will stay in place for 5 hours. One of the catheters will also be
      used to infuse stable isotopes.

      ii) Stable Isotopes Stable isotopes of amino acids are naturally occurring and are not
      radioactive. Stable isotopes are very similar to regular amino acids, except that they are a
      slightly heavier form (e.g., "heavy water" is a stable isotope of regular water). Stable
      isotopes are already present in very small quantities in your body. For 5 hours (6am - 11am),
      we will infuse stable isotopes into a forearm vein to increase the naturally occurring level
      by 7-10%. We will later be able to measure this change using highly sophisticated
      instruments. This will allow us to calculate the rate at which body builds muscle.

      iii) Muscle Biopsies During each of the visits, we will have either 2 or 3 muscle biopsy
      samples taken directly from 2 small incisions in the muscle of the thigh. On visit 1, we will
      have biopsies at 2 time points and on visit 2 there will be 3 biopsies. The muscle biopsy
      procedure involves the taking of a small piece of muscle tissue from the outside of the upper
      leg, about 4-6 inches above the knee. The skin is cleaned and injected with local anesthetic
      (lidocaine, a numbing medicine) to minimize any pain. A small incision about 1 cm will be
      made in the skin, through which a needle about 0.8 cm is advanced into the muscle. A piece of
      the muscle is then removed with the needle, the skin is closed with a special medical glue or
      suture, a dressing is applied and pressure on the biopsy site held for about 10 minutes to
      stop any bleeding that might occur. The leg is then wrapped in an ACE bandage to prevent any
      bleeding that might occur.

      iv) PET/CT Scan In between the biopsies, the volunteer will be injected into a vein with a
      dose (12.5 millicurie) of L-[methyl-11C]methionine (11C-MET) to begin the PET/CT imaging.
      Like the stable isotope talked about in section "ii" above, methionine is a naturally
      occurring amino acid in the body. However, the form of methionine is radioactive (this allows
      the scanner to detect its presence in your body). The PET/CT will take detailed pictures of
      the flow of 11C-MET into the muscles of the legs, which will provide information about new
      muscle protein being formed. The volunteer will need to lie still on a table with the thighs
      inside the machine. The table will move and the machine will make clicking and whirring
      noises as the pictures are taken. It will take about 90 minutes to gather the scan data.

      v) Ingestion of protein drink Towards the middle of the 2nd visit, the volunteer will be
      asked to drink approximately 8 fluid ounces of a drink that contains 15 grams of protein.
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Healthy women
      
Biospecimen description: 
      Biopsies will be taken from upper thigh, Muscle tissue