Acute Myocardial Infarction Clinical Trial
Official title:
68Ga-NODAGA-E[c(RGDγK)]2: a Novel Positron Emission Tomography (PET) Tracer for in Vivo Molecular Imaging of Myocardial Angiogenesis Following Myocardial Infarction
The aim is to examine the expression of αvβ3 integrin using a novel selective radiotracer in patients with myocardial infarction and investigate if it is a suitable tool for predicting myocardial recovery and thus prognosis.
Ischemic heart disease is worldwide the single most frequent cause of death. The number of
patients surviving acute myocardial injury is increasing due to improved acute treatment.
However, after the initial repair, the tissue undergoes a remodeling phase to compensate for
the damaged area. This re-modeling phase can change the structure end geometry of the heart
resulting in lower ejection fraction, leading to cardiac dysfunction, which eventually leads
to heart failure. Understanding and ideally modifying the reparative mechanisms following
myocardial infarction is increasingly important and may lead to improved outcome.
If the heart suffers from ischemia following an acute coronary event, the tissue reacts
strongly to the hypoxia. The body will as a compensatory mechanism create new vessel to
provide the tissue with oxygen. This is known as the biological process of angiogenesis. This
complex process involves different angiogenic and pro-fibrotic transcription factors that
initiate the restoration of capillaries by sprouting from the existing endothelial cells in
response to hypoxia.
Time seem essential to protect and save the myocardium. An early onset of cytokines and
growth factors is associated with a decline in cardiomyocytes apoptosis, smaller infarct
areas, and decreased ventricular dilation. Therefore, an early induction of angiogenesis
seems important for a good prognosis of the patient.
Integrin αvβ3 is a transmembrane cell surface receptor that is markedly upregulated in states
of angiogenesis. It facilitates migration and proliferation and thereby allowing cells to
respond to extracellular environment. Integrin αvβ3 is thus a key player in the angiogenic
process. The integrin αvβ3 has a binding site for an RGD peptide (Arg-Gly-Asp motif) and this
can be targeted by PET tracers.
RGD-based PET tracers have been shown to accumulate at the site of myocardial necrosis in
both human and animal studies. The uptake seems to peak a few weeks after the infarction and
may correlate to recovery of cardiac function and thus serve as a prognostic marker.
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