In Vivo Molecular Fluorescence Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 257

electrical, and chemical behaviors of nano-scale range materials are different from
the same materials at larger scale range. Nanotechnology is a good candidate to solve
fundamental problems of the current drug industry such as poor solubility and lack
of target specificity. Since the size of the smallest capillaries is around 5-6µm,
nanoparticles are a promising agent for intravenous drug and imaging agent delivery.
In cancer, in particular, due to leakiness in the tumor vascularization, these particles
can easily penetrate the tumor and be accumulated inside [3]. Nanoparticles can be
used to internalize drugs through epithelial and endothelial barriers. For example,
due to the blood-brain barrier, many therapeutics and contrast agents cannot reach
the brain; therefore, smaller molecules and nanoparticles are needed to pass through
these barriers [4]. Another advantage of nanoparticles is their capability to deliver
drugs specifically to particular cells, locations, or organs. They are also capable of
codelivering two or more drugs at the same time.
recent discoveries in cancer and other disease-related biomarkers and the suc-
cessful treatments by drugs that selectively target those biomarkers (such as mono-
clonal antibodies (mAbs) [5, 6]) have created a new demand for developing better
molecular imaging probes and improving the in vivo imaging systems. These imaging
techniques can be used to trace the drug delivery path inside the body and to monitor
the efficacy of therapeutic agents, especially at the early stages of treatment. In
clinical studies, the current gold standards for the detection of disease-specific bio-
markers are primarily based on ex vivo methods, such as immunohistochemistry
(IHC), fluorescence in situ hybridization (FISH), and enzyme-linked immunosorbent
assay (elISA) [7-9]. All these methods require several biopsies from the lesion.
However, usually due to heterogeneity of the lesions, a few biopsies cannot cover the
whole lesion, and some parts may be left uncharacterized. Also, during the therapeutic
cycles, the number of times that a biopsy can be taken is limited. The current goal is
to replace these invasive methods with noninvasive techniques to image the tissue
while it is still intact and in its natural environment.
In many cases, there is a need to use contrast agents to improve the signal-to-noise
ratio and specificity to the targets, since it is difficult to distinguish between the
tumor and benign tissues only from their structural differences. Targeted molecular
probes can be used to differentiate the tumor from normal tissues, based on their
molecular specifications, in vivo [10, 11] or in clinical surgery [12-14].
The design of each contrast agent depends strongly on the imaging technique.
In optical imaging, each imaging technique requires different characteristics for its
contrast agent. For example, optical coherence tomography (oCT) images the back
reflection photons from different layers of the tissue; therefore, it needs contrast
agents that can improve the scattering properties of the target. on the other hand,
high absorption and high quantum yield are desired properties for the contrast agents
in photoacoustic tomography [15-17] and fluorescence imaging, respectively.
This chapter focuses mainly on in vivo optical imaging techniques for fluorescent
nanoparticles as exogenous contrast agents. These noninvasive in vivo methods
allow the detection of the emitted photons from fluorescent contrast agents inside
the tissues. exogenous fluorescent probes can be designed as nontargeted contrast
agents, which circulate intravenously inside the body and accumulate in malignant