MRI with Gadolinium-Based Nanoparticles - Nanotechnology for Biomedical Imaging and Diagnostics - page 237

Gd 3 n@C 80 -[dipeG5000(OH) n ] and Gd 3 n@C 80 (OH) 26 (CH 2 CH 2 COOM) 16 , respec-
tively (M = H or na) [145, 151].

8.3.4.2 Gadonanotubes The use of carbon nanotubes as carriers for Gd 3+ was
first suggested by sitharaman et al . [152]. nanotubes in the 20-100 nm size range
seem suitable for cellular uptake and exhibit favorable biocompatibility. Furthermore,
they can be derivatized at the exterior while sequestering the substance of interest in
the interior. The so-called gadonanotubes were produced by sonication of ultrasmall
(us) tubes in aqueous GdCl 3 . The resulting compounds exhibited highly improved
relaxivities as compared to the approved Gd-based CA, with r 1 values 40-fold higher
under clinically used magnetic field conditions and up to 90-fold higher at lower
fields. The mechanisms by which the relaxivity is strengthened appear to be differ-
ent from the fullerene ones because in the case of gadonanotubes, no aggregation of
the particles occurs. Furthermore, the Gd 3+ is directly exposed to water in this case,
and this is the very efficient access to water in the nanotubes, which are known
to be good transporters of water, that would contribute to enhancing relaxivity.
Interestingly, pH dependency of the relaxivity was observed with a dramatic
decrease from pH 7 to 7.4, suggesting possible applications in pH mapping [153].
In vitro studies have highlighted the internalization properties in various cell lines
such as stem cells [154] or macrophage cells, [155] and functionalization of the
surface of the tubes with serine were efficient for labeling MCF-7 human breast
cancer cells [156]. In vivo studies were initiated with gadonanotubes incorporating
biodegradable polymers in order to assess the biocompatibility of these new
materials [157, 158]. These preliminary results suggested limited toxicity of these
compounds, but more experiments will be necessary to make sure that the use of this
new class of CAs is safe for human use.

8.3.5 other new emerging Gd nanoparticles

8.3.5.1 Gold Nanoparticles Gold nanocrystals can be easily functionalized on
their surface by thiol derivatives. When loaded with Gd 3+ , they can be used as multi-
modal agents with the properties of Gd 3+ for MRI and the properties of the gold
core for X-ray imaging and radiotherapy [159]. The process used in the prepara-
tion of paramagnetic gold nanoparticles (Gnps) involves the reduction of a gold
salt (HAuCl 4 ) by the thiol-containing Gd 3+ -dTpA derivative [160] (Fig. 8.7). This
method leads to the production of 2-2.5 nm Gnp coated with approximately 150
Gd 3+ complexes and r 1 = 585 mM −1 s −1 . The use of a Gd 3+ complex bearing a thiol at
both extremities, as proposed by park et al ., allowed the introduction of the ligand
in polymerized form with a very large gadolinium payload (~10,000 Gd/particle,
5-7 nm in size; see Fig. 8.7) [161, 162]. Investigations to improve the relaxivity of
Gnps showed that bigger particles tend to decrease the tumbling rate of the Gd 3+
complex, thus increasing r 1 . Also, it was shown that overcoating the Gnps with
multilayers of oppositely charged polyelectrolytes restricted the motion of the Gd 3+
chelates and improved the relaxivity [163]. In vivo studies highlighted the potential
of these particles as blood pool agents without undesirable accumulation in the