MRI with Gadolinium-Based Nanoparticles - Nanotechnology for Biomedical Imaging and Diagnostics - page 238

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HAuCl 4 HAuCl 4

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FIGuRe 8.7 preparation of Gd-loaded gold nanoparticles with monochelate (left) or
polymerizable chelate (right).

lungs, spleen, or liver [162]. They have also been derivatized for targeting by means of
antibodies [164], biotin [165], or dnA for cellular uptake [166].

8.3.5.2 Viral Capsids When the genome of viruses is removed, the resulting virus
capsids become noninfectious and unable to replicate. But, because they can still
access cellular materials, they have been suggested by douglas and Young as carriers
for drug delivery or bioimaging applications [167]. Virus capsids are made of proteic
subunits, with a vacant interior that can be used to entrap substances of interest and
the exterior that can be modified chemically. Furthermore, genetic engineering
allows modifications of the subunit for modulation of the architecture or metal
binding [168]. The first example of Gd 3+ -loaded virus was described by Allen et al .
who used cowpea chlorotic mottle virus (CCMV). The presence of 180 binding sites
for Ca 2+ in the interior was used to introduce approximately 140 Gd 3+ per particle
with a resulting relaxivity of 202 mM −1 s −1 at 61 MHz, which is approximately 25-fold
higher than monomeric Gd 3+ chelates [169]. However, the low binding affinity of
Gd 3+ ( K d = 31 μM) precludes any in vivo application. In order to improve the Gd 3+
sequestration in such structures, the surface of the capsids has been conjugated to the
well-known ligands dTpA [170] and dOTA [171], with 100-500 Gd 3+ incorporated
per viral particle. The measured relaxivity was two- to threefold that of Gd 3+ -dTpA.
However, these values are too low if we consider the overall weight of the viral
capsid (~2000 kda in this case) and the resulting dose that would be necessary to
obtain a good contrast enhancement. Improvements under investigation are the
incorporation of the Gd 3+ complex on the interior surface of the capsid, which was
shown to produce 30-50% increase in the relaxivity with HOpO-like ligands [172].
Also, when the rigidity of the linker between the capsid surface and the HOpO
ligand was increased, better relaxivity was obtained [173]. The behavior of these
particles in cell culture and in vivo should provide in the near future indications on
their immunogenicity and on their potential applications.

8.3.5.3 Gadolinium Oxide Nanoparticles While most of the gadolinium-based
CAs incorporate the paramagnetic species in the ionic form (Gd 3+ ), the idea to use the
oxide form Gd 2 O 3 has emerged recently. The first species were prepared as a Gd 2 O 3
core capped with diethylene glycol (deG). The relaxivity was two to three times