Plaque at risk (ParisK): Molecular imaging of plaque vulnerability using 18F-choline PET-MRI in patients with carotid artery atherosclerosis

The possibility of the identification of the risk of rupture of a carotid
plaque will have tremendous impact in clinical decision making. Firstly, in
symptomatic patients with a 30-69% stenosis, who are currently not operated
upon according to the current guidelines, identification of the risk of rupture
plaque could identify patients who have a high risk of recurrent stroke, and
would, therefore, benefit of carotid intervention, such as endarterectomy or
stent placement. This could potentially prevent a substantial number of
strokes. Secondly, in all symptomatic patients with a 80-99% stenosis carotid
intervention should be considered, according to the guidelines. However, only
one out of six patients with a 80-99% stenosis benefits from a carotid
intervention. Identification of patients with a high risk of a recurrent stroke
would reduce the number of unnecessary interventions substantially. Hence, a
diagnostic imaging test with high accuracy for recurrent stroke prediction has
tremendous clinical impact in patients with carotid artery disease.
Previous studies have evaluated the use of imaging to assess carotid plaque
vulnerability, mostly showing a good correlation between imaging and histology
and/or clinical characteristics. Plaque vulnerability is defined by a large
necrotic core, a thin fibrous cap and, importantly, by the presence of
intraplaque inflammation. However, previous studies have focused on single
modalities (magnetic resonance imaging [MRI], multidetector-row computed
tomography [CT], or ultrasonography, have used relatively small cohorts. This
could be the reason why carotid artery imaging studies so far have not changed
the therapeutic guidelines. In addition, the imaging modalities so far may not
have delivered the necessary sensitivity to achieve the goal of changing the
guidelines.
18F-choline is a tracer used for years now in oncologic imaging. However, only
recently experimental data has shown that the tracer is a sensitive tool to
imaging active inflammation, including atherosclerosis in animal models.
Therefore, 18F-choline will be tested in a clinical trial on (n=25) patients
with a symptomatic carotid artery stenosis due to atherosclerosis.
Participating patients will undergo 18F-choline PET-MRI as well as FDG PET of
the plaque. Imaging will be correlated with histology.

Primary:
-The correlation between 18F-choline uptake in the atherosclerotic plaques on
PET-MRI and plaque inflammation on histology, including the content of
CD68-positive activated monocytes/macrophages.

Secondary:
-The correlation between the degree of 18F-choline uptake on PET with(in) the
fibrous cap status, areas of micro-calcifications, and areas of the lipid-rich
necrotic core of the atherosclerotic plaques as assessed by histology;
-The correlation between 18F-choline uptake as assessed by PET-MRI and FDG
PET-MRI parameters of plaque vulnerability;
-The association between the degree of 18F-choline uptake on PET with the
cardiovascular risk profile and history of patients.

Prospective study.

Single dose administration of the study drug -18F-choline- a radiotracer for
PET imaging.

Burden:
-During the PET-MRI examination, patient lays for 30 minutes in the scanner,
followed by 2 short additional scans of 10 minutes each. This does not have to
be a problem, but it can be difficult for patients with back problems.
-The PET-MRI scanner is a kind of tube, with openings in the front and back.
Still, some patients may feel uncomfortable when laying in the tube.
-The PET-MRI scanner produces a lot of noise during the examination, which can
be unpleasant for the patient. Therefore, participating patients will use a
protecting head set or ear plugs.
-During the PET-MRI examination, the 18F-choline tracer and possibly MRI
contrast agent (in patients without contra-indications) will be intravenously
administered; patients can experience a warm feeling.
-During FDG PET, the FDG radiotracer is administered intravenously, followed by
an about 30 minute scan.

Risks:
-PET examination is not harmful for one*s health. However, PET uses ionizing
radiation. The radiation dose of 18F-choline PET is approximately 8 mSv. The
MRI contrast agent is associated with a low rate of side effects. In severe
cases, contrast-induced nefropathy could occur; however, this is unlikely to
occur as patients with impaired renal function will not receive injection of
the MRI contrast medium. Therefore, the use of the MRI contrast agent is
relatively safe and adverse effects rarely occur. At the place of injection of
tracer and possibly the contrast agent, (temporary) bruising or swelling may
occur, and the place may be sensitive. In extremely rare cases, an infection
could occur at this place.
-MRI does not using ionizing radiation. Patients with pacemakers, metal
implants, vessel clips, or metal splinters in the eye will not be scaned in the
MRI.