Noninvasive Imaging of Vulnerable Inflammatory Coronary Plaque using Cardiac PET/CT in Humans: a feasibility study

Coronary artery disease (CAD) is the leading cause of death in the western
world. Traditional strategies for the detection and treatment of CAD are aimed
at detecting flow limiting coronary atherosclerotic lesions and subsequently
restoring coronary flow either by percutaneous coronary intervention (PCI) or
coronary artery bypass grafting (CABG) for symptom relief. Although this
strategy is suitable for patients with stable CAD, it does not identify
patients at risk to develop an acute coronary syndrome (ACS). The latter
syndrome is caused by coronary plaque rupture provoking thrombosis leading to
unheralded events such as unstable angina and myocardial infarction.(Naghavi et
al. Circulation 2003, Finn et al. ATVB 2010) These plaque ruptures often occur
in non-obstructive lesions, which generally outnumber symptomatic stenotic
plaques.(Libby et al. Circulation 1995) Consequently, an ACS with potential
devastating effects is frequently the initial presentation of CAD in previously
asymptomatic patients. Next to obstructive severity, therefore, plaque
morphology assessment could play a pivotal role in the evaluation of CAD to
predict plaque stability.
Imaging of plaque biology and constitution is therefore of interest to
potentially identify those lesions that are prone to rupture. Positron emission
tomography (PET), in conjunction with a positron emitting labeled compound of
interest, allows to track biochemical pathways in vivo noninvasively. Studies
using PET have documented that the positron-labeled glucose analogue
18F-fluorodeoxyglucose (18F-FDG) is actively taken up in atheromata of the
carotid arteries and aorta.(Rudd et al. Circulation 2002, Rudd et al. J Nucl
Med 2008) Thus, increased uptake of 18F-FDG may provide a marker for
metabolically active inflammatory cells in plaque. Unfortunately, attempts to
use 18F-FDG PET for detection of inflammatory coronary plaques have been
disappointing.Therefore novel probes are required to specifically visualize the
biological characteristics of the coronary vulnerable plaque that are not
metabolized by the myocardium itself and yield a sufficient
target-to-background ratio. In recent years, several tracers have been
developed for this purpose. Among these are tracers that bind to macrophages
(11C-PK11195), matrix-metalloptroteinase (18F-AS101), or integrins
(18F-galacto-RDG).(Lamare et al. J Nucl Med 2010, Quillard et al. ATVB 2011,
Laitinen et al. Circulation Cardiovasc Imaging 2009) Each of these probes has
demonstrated their ability to detect inflammatory atheromata in animal
experiments. In addition, human studies have showed that 11C-PK11195 can also
be detected with PET in inflamed carotid artery plaques.(Gaemperli et al. Eur
Heart J 2012) Studies to evaluate the feasibility to image coronary vulnerable
plaques are, however, lacking.

The objective is to study the feasibility of different PET tracers to detect
vulnerable plaques in patients with a recent acute coronary syndrome and
co-localize these inflammatory lesions with anatomical plaque features obtained
with CT based coronary angiography (CCTA).

Twenty-four patients (35-75 years) admitted to the coronary care unit with an
ACS and no prior history of percutaneous coronary intervention, coronary artery
bypass surgery, or myocardial infarction will be included. Prior to ESC
guidelines indicated ICA all patients will undergo a PET/CT-scan. The scanning
sequence will consist of a CCTA, which will be fused with PET images using an
investigational tracer to potentially identify the vulnerable plaque. In a
serial manner, each tracer will be tested for feasibility purposes in eight
patients per tracer (either 11C-PK11195, 18F-AS101, or 18F-Galacto-RGD). Tracer
kinetics will be quantified and co-registered with the coronary tree as
obtained with CCTA. After PET/CT, ICA will be performed in combination with
optical coherence tomography (OCT) to identify vulnerable plaque invasively.
PCI will subsequently be performed according to the current ESC guidelines on
myocardial revascularization.

PET-tracer (11C-PK11195, 18F-AS101, or 18F-Galacto-RGD)

Patients will receive contrast during CCTA with risk of allergic reactions or
renal failure. Renal function will be tested during regular care and will be
available for considering participation. All patients with estimated glomerular
filtration rate < 45 ml/min will be excluded to avoid any risk of renal
failure. During CCTA one of the investigator will be present to monitor any
allergic effects to the contrast agent. Appropriate measures will be executed
when necessary. Patients will receive 6 * 8 mSv during PET/CT protocol. There
will be no direct benefit to participate in this study for patients
individually. Improvement of clinical healthcare is the main purpose of this
study and is considered beneficial by the investigators.