This study will test whether positron emission tomography (PET) imaging can be used to
measure blood flow to joints in patients with rheumatoid arthritis (RA). It will also
compare blood flow measurements using PET with measurements obtained with magnetic resonance
imaging (MRI) to determine how useful MRI is in measuring blood flow to joints.
Much of the joint damage in RA is caused by the synovium-the lining of the joint. In RA,
the synovium increases in size and destroys bone and cartilage. The synovium maintains its
growth by forming many new small blood vessels to nourish it. New drug treatments are being
developed to stop the growth of these new blood vessels. The effect of these treatments on
the synovium is usually measured by performing a biopsy-removing a small piece of synovium
for examination under a microscope. The biopsy requires inserting a needle into the joint
to withdraw the synovial tissue. This study will see if changes in blood flow can be
assessed accurately using noninvasive imaging procedures, such as PET scanning, instead of a
Patients 18 years of age and older with rheumatoid arthritis who have at least one tender
and swollen knee due to synovitis may be eligible for this study. Candidates will be
screened with a medical history and physical examination.
Participants will have a mold made of the knee to be studied and will have routine blood
tests. Women who are able to become pregnant will have a pregnancy test. All participants
will then undergo PET and MRI scanning as described below:
PET - A needle is used to insert a catheter (small plastic tube) into an arm vein for
injection of the radioactive substance H215O. The patient lies in a doughnut-shaped machine
(the PET scanner) and a quick scan is done to measure body thickness. Then, a separate scan
is taken following each of six or fewer injections of H215O. Each scan lasts about 13
MRI - The patient lies on a stretcher that is moved into a cylinder containing a magnetic
field (the MRI scanner). A special coil is placed over the knee to improve the quality of
the images. Earplugs are worn to muffle the loud thumping sound produced by electrical
switching of the magnetic fields during the imaging. A contrast agent called gadolinium is
injected through a catheter into a vein to improve the quality of the images. An intercom
system permits the patient to communicate with the technician at all times during the
Because of the proliferative nature of rheumatoid synovial tissue, many new pharmaceuticals
are targeting angiogenesis inhibition as a means of halting synovial growth. Although
clinical markers of rheumatoid arthritis (RA) activity may function as surrogate endpoints
in trials of these new agents, a non-invasive technique of assessing synovial blood flow
would be the ideal outcome measure.
PET imaging has been used to quantify blood flow to a variety of tissues, with significant
experience at this institution in the area of tumor blood flow analysis.
The objective of this study is to evaluate the feasibility of H2 (15)O PET for the
measurement of synovial blood flow in patients with RA. In 10 RA patients with active knee
synovitis, clinical and radiological (H2 (15)O PET and dynamic MRI) evaluation will be
performed. The feasibility of H2 (15)O PET will be evaluated by its reproducibility. We
will also evaluate the correlation of dynamic MRI with synovial blood flow measurement by H2
18 years of age or greater.
Must meet the American College of Rheumatology's diagnostic criteria for RA(21).
Must have or have had synovitis in at least one knee characterized by tenderness,
swelling, or effusion within 30 days prior to screening.
Women must test negative on a pregnancy test unless they are post-menopausal or surgically
Patients with concurrent known bacterial, septic, or crystal-induced arthritis, or with
other rheumatic diseases that may confound the analysis including but not limited to Lyme
disease, psoriatic arthritis, spondylarthropathy, systemic lupus erythematosus, or
Patients who would be beyond the guidelines for radiation exposure from research studies
within the past year.
Patients who exceed the size or weight limitations of the PET or MRI scanner.
Patients who suffer from claustrophobia or who have any of the following: cardiac
pacemakers, auto defibrillators, neural stimulators, aneurysm clips, metallic prostheses,
cochlear (ear) implants, any implanted devices (pumps, infusion devices, etc), metal
fragments in the eye, or shrapnel injuries.
Any musculoskeletal, neurological, or vascular condition that may alter the normal
function and structure of knee joint of interest or will interfere the patient's ability
to undergo study-related intervention and imaging.
Any clinically significant medical condition that, in the opinion of the investigator,
would pose added risk for study participants.
History of allergic or non-allergic serious reaction to gadolinium, or H2 15O PET.
Pregnant women or nursing mothers.