Biomedical Engineering Reference
In-Depth Information
as having the potential to make paradigm-changing impacts on the detec-
tion, treatment, and prevention of cancer. The growing interest in nanotech-
nology by both academic and industrial investigators has led to increased
development of novel nanotechnology platforms for medical applications,
sharp increases in government funding, and venture capital investment. In
the cancer context, nanotechnology will lead to a new generation of diag-
nostic and therapeutic technologies, creating a range of new solutions for
diagnoses and treatment of neoplastic diseases [4-5, 26, 70-73].
Diagnostic methods are essential for the early detection of diseases to
enable their prompt treatment, minimizing possible damage to the rest of
the organism. Conventional imaging technologies represent static images
of tumors, rather than a continuous visualization of tumor proliferation.
Nanodiagnostics, defined as the use of nanotechnology for clinical diagnos-
tic purposes [74], was developed to meet the demand for increased sensi-
tivity in clinical diagnoses and earlier disease detection. NP-based systems
imaging allows an early detection of tumor, as well as opportunities for
real-time monitoring, thereby increasing both the sensitivity and accuracy
of anticancer therapies. Initial results in nanotechnology-enabled molecular
imaging have been made in all imaging modalities, including optical, nu-
clear, ultrasound, computed tomography, and magnetic resonance imaging
(MRI). MRI contrast agents have made a significant impact in the use of
MRI for various clinical indications. MRI contrast agents contain paramag-
netic or superparamagnetic metal ions that affect the MRI signal properties
of surrounding tissue. These contrast agents are used primarily to increase
the sensitivity of MRI for detecting various pathological processes and also
for characterizing various pathologies. In addition, the contrast agents are
used for depicting normal and abnormal vasculature, or flow-related abnor-
malities and pathophysiologic processes like perfusion. A conglomerate of
numerous nano-sized iron oxide crystals coated with dextran or carboxydex-
tran forms superparamagnetic iron oxide (SPIO) contrast agents [75]. Two
SPIO particle formulations are now clinically available, namely ferumoxides
and ferucarbotran. Both are approved specifically for MR imaging of the
liver. After intravenous administration, clinical approved SPIO particles are
cleared from the blood by phagocytosis accomplished by reticuloendothelial
system so that uptake is observed in the normal liver, spleen, bone marrow,
and lymph nodes. After the intracellular uptake, SPIOs are metabolized in
the lysosomes into a soluble, nonsuperparamagnetic form of iron that be-
comes part of the normal iron pool [75]. Following intravenous injection,
SPIO is incorporated into macrophages via endocytosis. The uptake of
SPIO by phagocytic monocytes and macrophages provides a valuable
in-
vivo
tool by which MRI can be used to monitor involvement of macrophages
in inflammatory processes, such as multiple sclerosis, traumatic nerve injury,
stroke, brain tumors, and vulnerable plaque in carotid artery. Neuwelt et al.
[76] conducted clinical studies with MRI monitoring of macrophages in
