Biomedical Engineering Reference
In-Depth Information
the ischemic process, the authors were able to determine the temporal expression
of the proteins targeted and, in a novel application, to investigate the relationship
between protein expression and blood l ow by simultaneously performing
perfusion imaging using untargeted lipid microbubbles.
Ultrasound molecular imaging has also shown promise outside of the potential
applications to cardiovascular disease. By using microbubbles targeted to ICAM-1
and VCAM-1, Reinhardt
et al.
(2005) were able to both depict and quantify
inl ammation in the brain and spinal cords of rats in experimental autoimmune
encephalitis (EAE) using an enhanced technique, Sensitive Particle Acoustic
Quantii cation (SPAQ). In a separate model, Palmowski
et al.
(2008) used
microbubbles linked to α
v
β
3
integrin binding ligand to examine angiogenesis in a
mouse model of squamous cell carcinoma.
h e main challenge to the future clinical translation of ultrasound molecular
imaging is the need for further improvements in probe and transducer design;
future research will be directed towards this end.
MOLECULAR MRI OF ENDOTHELIAL ADHESION
MOLECULES
Molecular MRI
(mMRI) is an attractive method for imaging of endothelial
adhesion molecules for a number of reasons: it is non-invasive, of ers high spatial
resolution and signal-to-noise ratio, and provides excellent sot tissue contrast.
h e main challenge of mMRI, compared to nuclear or optical imaging techniques,
is its inherently low sensitivity. However, the use of paramagnetic (Gd-based)
or super-paramagnetic (iron oxide-based) nanoparticle MR contrast agents can
overcome this limitation to generate positive or negative or contrast enhancement.
Initial attempts to create a targeted mMRI contrast agent involved conjugating an
antibody against the epitope of interest to a traditional MR blood-pool contrast
agent, such as
gadolinium
diethylene-triamine-penta-acetic acid
(Gd-DTPA).
However, the major limitation of Gd-based agents is that only a small quantity
of Gd can be delivered to an endothelial monolayer, resulting in modest contrast
ef ects, and to address this more recent agents have used multiple Gd complexes
per antibody-conjugated nanoparticle (Doiron
et al.
2008). To further improve
contrast signal, novel imaging agents and epitope-binding ligands with higher
ai nity have subsequently been developed to overcome the limitations of a Gd-
based approach. h ese are described in detail below.
h e conjugation of
microparticles
and
nanoparticles
with monoclonal antibodies
shows promise as a method of detecting endothelial adhesion molecular expression
using mMRI. Sipkins
et al.
(2000)reported the detection of ICAM-1 upregulation
on the cerebral microvasculature of mice with EAE by
ex vivo
MRI (9.4 T) using
antibody-conjugated paramagnetic liposomes (ACPLs). In 2002, Kang
et al.
successfully demonstrated the expression of E-selectin
in vitro
in human endothelial
cells using the F
ab
fragment of anti-human E-selectin monoclonal antibody
conjugated to cross-linked iron oxide nanoparticles. More recently, McAteer
et al.
