MRI with Gadolinium-Based Nanoparticles - Nanotechnology for Biomedical Imaging and Diagnostics - page 233

dendrimers have also been conjugated to several small targeting molecules such as
folate that is directed against folate receptor expressing ovarian cancers [109-111],
CLT1 peptide targeting the fibrin-fibronectin complexes in tumor [112], or an
RGd-cyclopeptide targeting integrin α V β 3 [113]. Also, peGylation of the surface of
a dendrimer combined with the conjugation to peptide T7 targeting transferin highly
expressed in brain and liver tumor led to enhancement of the imaging of tumors in
the liver, but not in the brain [114].

8.3.3 lipid-Based nanoparticles

8.3.3.1 Structure and Relaxivity Liposomes and their derivatives can be obtained
with various sizes and degrees of functionalization, allowing delivery of drugs or
imaging agents to many targets of interest (see Chapter 3). The first type of liposome-
based MR CA described contained the paramagnetic species in the aqueous inner core
(Fig. 8.6a). However, Gd 3+ -dTpA entrapped in such systems produced limited ionic
relaxivity, lower than the free Gd 3+ -dTpA. These disappointing results were attributed
to the reduced water exchange at the Gd 3+ due to the slow diffusion of water molecules
through the lipidic layers. It was also shown that relaxivity was highly influenced by
the liposome size with smaller liposomes exhibiting better results due to a larger
surface area to volume ratio or by the membrane composition and its permeability [115].
nonetheless, this low relaxivity could be advantageously used for pH-dependent
imaging systems as proposed by Løkling et al . who developed liposomes that are
stable at physiological pH but disaggregate at lower pH, thus releasing the Gd 3+ -dTpA
that once free would exhibit a higher relaxivity to the surrounding tissues [116].

(a) (b) (c)

(d) (e)

Gd 3+ complex
Polar head

19 F

Hydrophobic tail
Polymer

FIGuRe 8.6 schematic representation of (a) liposome with Gd 3+ complex in the aqueous
core, (b) liposome with Gd 3+ complex incorporated into the lipid bilayer, (c) micelles, (d) liposome
with Gd 3+ complex at the exterior, and (e) perfluorocarbon nanoparticles.