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peripheral arterial disease and myocardial infarction.
Imaging angiogenesis would therefore be valuable in
assessing risk stratification of patients with arterial
occlusive disease.
Selected Examples of Molecular Imaging Probes.
The biodistribution of molecular imaging probes is
determined by specific interactions between the
radioactive molecule and its target, which can be for
example antigen, enzymatic or receptor-binding.
Therefore the probe should present a high affinity to
its target, and also a high specificity, resulting in its
selective uptake and distribution at the target tissues.
Different types of biomolecules and
radionuclides, both metallic and non-metallic, have
been explored in nuclear imaging.
Within the field of cardiac molecular imaging
fluorine-18 fluorodeoxyglucose (
18
F-FDG) is the
most widely used agent (Figure 4).
18
F-FDG is a radiolabeled glucose analogue
transported into metabolically active cells, and
therefore it is an ideal agent for the assessment of
viable myocardium.
Moreover,
18
F-FDG presence is also correlated
with plaque macrophage content, and, therefore,
could be used as a surrogate reporter of this critical
cell involved in atherogenesis and plaque rupture
(Osborn, Jaffer, 2012).
Figure 4: Structure of
18
F-FDG.
The renin-angiotensin system (RAS) plays an
important role in regulating blood volume, arterial
pressure, cardiac and vascular function, and may
contribute to the pathogenesis of atherosclerosis.
The renin-angiotensin system is frequently activated
early in heart failure and is linked to left ventricular
remodeling and myocardial fibrosis.
A comprehensive in vivo approach to the study
of the RAS and its many components has been made
difficult by the complexity of the system. However,
this system has, at the same time, provided a number
of targets for nuclear imaging via radiolabeled
ligands, with special emphasis on the angiotensin-
converting enzyme (ACE).
The initial attempts at developing specific ACE-
binding radiotracers were made by use of
18
F–
labeled captopril, the first clinically available ACE
inhibitor. In normal rats, in vivo biodistribution at 30
minutes after injection revealed high uptake values
in the lungs, kidneys, and aorta, organs with known
high concentrations of ACE. This agent, however,
had a number of shortcomings that reduced its
potential as a suitable tracer for examining ACE
distribution, as it is believed to have a higher affinity
for vascular ACE than for tissue ACE and, thus, to
be less suited for examination of tissue-bound ACE
activity.
Another
18
F-labeled ACE inhibitor, lisinopril,
showed higher affinity for tissue ACE and allowed
higher resolution during in vitro autoradiography
when compared with
18
F-labeled captopril.
99m
Tc-
labeled lisinopril derivatives have been also
developed (Femia, et al., 2008) and recently it has
been shown that
99m
Tc-lisinopril localizes in the
heart of transgenic rats that over-express human
ACE-1 (Dilsizian, et al., 2012). The combination of
these studies has shown the feasibility of in vivo
imaging of ACE both by PET(
18
F) and SPECT
(
99m
Tc).
ACKNOWLEDGEMENTS
Fundação para a Ciência e a Tecnologia is
acknowledged for the Ciência 2007 grant to F
Mendes. The financial support of Covidien, Petten,
The Netherlands to IST/ITN is acknowledged.
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