Biomedical Engineering Reference
In-Depth Information
to deliver therapy with an anti-angiogenic drug, and to quantify the response to
treatment. h e authors used 1.5T MRI to i rst image the presence of angiogenesis
in the vasa vasorum of the aorta of rabbits fed a high-cholesterol diet. Rabbits were
then injected with a further round of nanoparticles of the same formulation but
containing fumagillin, a known anti-angiogenic agent, before further nanoparticle
imaging showed decreased vasa vasorum signal enhancement. Such local targeting
approaches allow the use of agents, such as fumagillin, that may not be used
systemically because of adverse side-ef ects.
A broad body of work therefore suggests that mMRI probes may be of future
use in vascular endothelial adhesion molecule imaging. For such probes to become
clinically useful, an important step will be ensuring the biocompatibility of these
agents in humans. h is in turn will require the ongoing development of imaging
probes that are capable of providing high imaging contrast while remaining
biodegradable and non-toxic. h e development of micron-sized biodegradable
contrast particles for clinical use is already underway.
RADIONUCLIDE BASED IMAGING: SPECT AND PET
In many ways, molecular imaging can be considered an extension of
nuclear imaging
techniques that use radiolabeled tracers to provide image contrast. More recently,
novel radiolabeled tracers targeted to specii c targets have been developed to study
vascular disease (Langer
et al.
2008). Compared to other imaging modalities, nuclear
imaging techniques such as positron emission tomography (PET) and single photon
emission computed tomography (SPECT) have the benei t of high sensitivity
and are thus able to detect low levels (picomolar range) of a specii c tracer (Saji
2004). A further advantage is the ability of nuclear imaging to provide functional
quantitative information, such as the density of a specii c protein marker (Langer
et al.
2008). However, spatial resolution of the technique, and hence anatomical
localization, are limited. In an early human application of molecular imaging,
Jamar
et al.
(2002) coupled the Fab fragment of an antibody against E-selectin with
99m
Tc, and used this probe to detect inl ammation in rheumatoid arthritis.
99m
Tc -
Fab uptake was not seen in normal joints, but was taken up by joints with synovitis
with a diagnostic accuracy of 88%. More recently, radionuclide imaging has been
used to image many of the biological processes responsible for atherosclerosis,
such as lipoprotein accumulation, apoptosis, and proteolysis (Langer
et al.
2008),
in animal models. Hua
et al.
(2005) constructed a
99m
Tc-labeled peptide targeted
at α
v
β
3
integrin to image angiogenesis in an ischemic hindlimb mouse model.
h e peptide selectively localized to endothelial cells in regions of increased
angiogenesis and could be used for serial tracking of the extent of angiogenesis.
Outside of the cardiovascular system, radionuclide nanoparticles have also been
used to image pulmonary endothelium and vascular brain tumors. For the former,
l uorescein isothiocyanate (FITC) labeled polystyrene latex nanoparticles (100 nm
