Nanotechnology and nanomedicine in cardiovascular therapy - Biomaterials and Devices for the Circulatory System - page 252

The generations with higher Gd 3+ content (G3 and G5) show prolonged
enhancement of tissue vasculature and are suited for non-tissue specifi c
imaging of sub-millimetre sized blood vessels (Yan et al. , 2005; Langereis
et al. , 2006). In a study comparing G1, G2 and G3 contrast agents, G3 agents
provided prolonged contrast enhancement in the heart and vasculature and
did so at a lower dose (Kaneshiro et al. , 2008). The creation of Gd 3+ den-
drimers has been followed by intra-generational modifi cations. Two differ-
ent G4 agents, bearing either an isothiocyanate or succimidyl ester moiety,
displayed equivalent organ vasculature enhancement although with differ-
ent clearance rates. This may allow greater fl exibility in contrast dose and
imaging time while using almost identical agents (Xu et al. , 2007).
The role of nanotechnology in MRI continues to be a rapidly expanding
fi eld as is exemplifi ed by the recent use of a gold and copper nanoshell in
an in vivo mouse model where it enhanced vascular contrast, but with a
dose-dependent toxic effect, indicating the need for more detailed investi-
gation (Su et al. , 2007).

9.2.6 Dual-mode imaging

Dual-mode imaging yields greater information than either method alone
by allowing the clinician to employ different imaging modalities (each with
its own advantages) highlighting different areas of interest while using a
single contrast agent. To aid this, nanostructures capable of functioning with
different imaging modalities settings would be very valuable in the clinical
setting.
In light of the advantages of MRI, most of the dual-mode nanoparticles
have been developed for use with MRI and another modality. Table 9.1
gives examples of such nanoparticles.
Other nanoparticles, not dependent on the use of MRI, are also being
investigated. They include an amine-functionalised quantum dot consisting
of three components: a VEGF protein, a macrocyclic chelating agent
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for VEGF
receptor recognition and 64 Cu labelling for PET imaging. This nanoparticle
has shown potential for dual PET and near-infrared fl uorescence imaging
of VEGF receptor recognition in a mouse model (Chen et al. , 2008).

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9.2.7 Nanotechnology-based imaging for atherosclerosis

Atherosclerotic plaque formation and rupture accounts for approximately
a third of deaths each year in the UK, through myocardial infarction,
ischaemic strokes, renal disease and limb loss. Early changes in vascular
architecture during atherosclerosis cannot be detected by current imaging
techniques. However it is possible that using the nanotechnology strategy