MRI with Gadolinium-Based Nanoparticles - Nanotechnology for Biomedical Imaging and Diagnostics - page 235

relaxivities (~2.5 × 10 6 mM −1 s −1 at 1.5 T) have been obtained [125]. The presence of
a high concentration of 19 F in the core makes them interesting for quantitative imaging
and spectroscopy in addition to the 1 H MRI [126].

8.3.3.2 Passive Distribution The pharmacokinetics of lipidic nanoparticles
depends on several factors such as their size, or the nature of the components of the
membranes that govern surface charge, permeability, and the degree of stabilization.
Gd 3+ liposomes have been reported to accumulate in the liver and spleen regardless
of the size and allowed detection of tumors in the liver with better results for the
smaller particles [127]. Because of their large size, they exhibit a longer blood
circulation time than single Gd 3+ chelates, especially when derivatized with peG,
allowing visualization of fine vasculature [128, 129]. Also, paramagnetic lipid-based
agents are the object of a growing interest for the visualization of atherosclerotic
plaque by various mechanisms [130-133].

8.3.3.3 Tissue-/Cell-Specific Contrast Enhancement with Lipid Nanoparticles
Micelles and liposomes incorporating peptides or antibodies on their surface have
been the object of several investigations. Morelli's group developed a series of peptide-
conjugated liposomes and micelles with potential targeting ability for somatostatin
receptors and interesting relaxivity properties [134, 135], although no investigation on
the in vivo behavior has been published yet. similarly, RGd peptide-conjugated lipo-
somes were developed by Kok et al . In vitro studies highlighted the ability of these CAs
to internalize in endothelial cells overexpressing the α v β 3 integrin cell surface receptor
[136]. Antibody-conjugated liposomes confirmed also their potential utility through
in vitro studies by Mulder et al . who demonstrated the binding properties of an antise-
lectin CA in cell culture [137] or in vivo by conjugation to the mAb 2C5 with significant
tumor contrast enhancement 4 h postinjection [138]. Another recent site-specific lipo-
some under investigation is a folate-targeted construct exhibiting faster and stronger
contrast enhancement in the targeted tumors than the nontargeted one [139].
Alternatively, systems have been developed with ability to exhibit their contrast
enhancement under specific conditions and allow particular physiological phenomenon
detection. For instance, a particularly ingenious system was proposed recently by
Figueiredo et al . consisting of the use of negatively charged liposomes aggregated
together with the positively charged protamine. In the presence of the enzyme of
interest, for example, serine protease in this case, digestion of the protamine and
subsequent release of the liposomes lead to an enhanced relaxivity [140]. Also, ther-
mally responsive paramagnetic lipidic structures have been developed allowing
three-dimensional tissue thermometry for monitoring in thermotherapy [141].

8.3.4 carbon-Based nanomaterials

8.3.4.1 Gadofullerenes Fullerenes are molecules made entirely of carbon in a
closed spherical shape. They have rapidly become interesting for sequestration of
metal ions due to the high inertness of the resulting metallofullerene structure.
Indeed, unlike metals complexed with chelating agents that are always in an