Chemistry Reference
In-Depth Information
alter the local optical properties of the tissue. This approach makes it possible to detect extremely low concentrations of
nanoprobes. Importantly, this method can take advantage of nanoprobes designed for other imaging modalities without
need for alteration.
In the first study,
in vivo
imaging of a preclinical mammary tumour was undertaken using MM-OCT and MRI [103].
Dextran-coated SPIONs were synthesised and conjugated with Her2 neu antibodies for tumour targeting. Tumour-bearing
mice were injected with targeted or untargeted SPIONs. MM-OCT showed accumulation of the targeted SPIONs in the
tumour. A high signal observed in the spleen due to the high concentrations of ferritin; however, the control animals showed
a similar signal. In the animal treated with non-targeted particles, high signals were observed in the liver, spleen, and lung.
MRI showed shifts toward lower
T
2
* values in the tumour when targeted nanoparticles were used. In the cases of non-
targeted particles or saline, the shifts were minimal (non-targeted) or to higher
T
2
* values (saline). This result suggests that
the targeting antibody successfully localises the SPIONs at the tumour.
In order to add additional modalities, protein microspheres were employed as the base for multimodal MM-OCT/MRI
imaging agents [104]. The hydrophilic protein shell consists of BSA surrounding a core composed of vegetable oil. SPIONs
(20-30 nm), Nile red, and vegetable oil were layered with an aqueous solution of BSA. The mixture was sonicated at 45°C
with surfactants. The product was centrifuged, washed, and filtered through a 5 μm filter. The cross-linked protein shell was
subjected to a layer-by-layer deposition of PDDA and silica, and functionalisation of the RGD peptide to target cells that
over-express integrin receptors. The final product was 2-5 μm in diameter.
In vivo
, the microspheres show negative
T
2
contrast enhancement in the MR image. MM-OCT allowed the accumulation
of targeted particles in the tumour to be observed in real time.
Ex vivo
MM-OCT confirmed that the RGD-targeted micro-
spheres accumulated in the tumour. Histology used the fluorescence of Nile red dye to show presence of microspheres in the
tumour tissue. These
ex vivo
results confirm that high-resolution, real-time
in vivo
imaging is possible using MM-OCT and
labelled protein microspheres.
16.9
photoacouStIc IMaGInG
The number of multimodal agents that include photoacoustic imaging has burgeoned in the past 2 years [105-115].
Photoacoustic imaging (PAI), the combination of optical and ultrasound imaging, is an emerging modality for noninvasive
detection of structural and functional anomalies in biological tissues, which can assist with image-guided therapy [108]. A
wide variety of nanoparticulate agents have been developed to include PAI capability, including gold nanotripods [110],
porphyrin-lipid-based supramolecular structures [111], single-walled and multi-walled carbon nanotubes [106, 109], as well
as multifunctional microbubbles and nanobubbles [107]. PAI is a natural, advantageous modality because commonly used
highly absorbing optical contrast agents, such as gold nanoparticles, gold-coated carbon nanotubes or Indocyanine green,
can be utilised. PAI offers high spatial resolution, a perfect complement to other modalities that suffer from low spatial res-
olution. For example, MRI can reveal tumour location and time-dependent behaviour of the nanoparticles, while PAI allows
delineation of tumour margin and vivid 3D visualisation of theranostic nanoparticles inside the tumour [112].
16.10
concluSIonS
It is clear that the ability to simultaneously interrogate anatomical features and biochemical processes by molecular imaging
has greatly increased our understanding of these important events. Visualising molecular processes
within
a living organism
in real time has become a key element of both basic research and diagnostic radiology. Combining the most powerful
imaging modalities to exploit their individual strengths overcomes the weaknesses of any individual technique. The advan-
tages of obtaining higher resolution images, sensitivity, and temporal resolution are obvious. Further, with the advent of
multimodal hardware, the development of multimodal imaging probes to facilitate co-registration has been critical for
optimising experiments.
In this chapter we have attempted to provide a snapshot of the many advances that have been made in demonstrating the
utility of multimodal nanoparticles for molecular imaging. While a great deal of progress has been achieved,
significant
hurdles remain. For example, a great deal of nanoparticle research is focused on controlling the size, stability, clearance, and
immunogenic properties of nanoparticles. Translation of these probes to the clinic faces the well-known problems of
long-term toxicity, pharmacokinetics, and pharmacodynamics of nanoparticle platforms. While many challenges remain, it
has become increasingly apparent that the benefits of using multimodal nanoparticles in basic research are just beginning to
be realised.
