Chemistry Reference
In-Depth Information
rapidly became the most extensively used system in the clinic. Gd-DTPA has been administered to more than
twenty million patients over a period of 10 years of clinical use. It is a very stable complex which distributes in the
blood and in the extravascular regions yet, thanks to its high hydrophilicity, is excreted by the kidneys on the time
scale of a few hours. In MR images, Gd-DTPA allows an excellent delineation of tumours.
A major challenge for MRI when the biological targets are present at very low concentrations is to achieve the
highest attainable sensitivity. One way to optimize the relaxivity is to use nanoscaffolds, such as dendrimers,
proteins, micelles, carbon-based nanosystems and metal-based nanoparticles. Two interesting examples involve
apoferritin, the use of which as a supramolecular template in nanotechnology was already discussed in Chapter 19.
A remarkably high relaxation enhancement (20-fold) of water protons has been observed for solutions containing
apoferritin loaded with Gd-HPDO3A (
Figure 22.13
)
. The entrapment of the complex within apoferritin allows an
increased number of dipolar interactions with water molecules and exchangeable protons in the protein cavity as
carrier for Gd(III) agents. This gadolinium-loaded ferritin can be targeted to tumour cells for use as a contrast agent
(
Figure 22.14
). The imaging procedure consisted of (a) targeting neural cell adhesion molecules with a biotinylated
FIGURE 22.14
Schematic representation of the adduct formed by C3d-Bio, streptavidin, and biotinylated Gd-loaded apoferritin (Gd-Apo-
Bio). The sequence of the dendrimeric C3d-Bio NCAM mimetic peptide is outlined.
(From
Geninatti Crich et al., 2006
. Copyright 2006 with
permission from AACR.)
derivative of C3d peptide, which is known to have high affinity for these epitopes, and (b) delivery of a streptavidin/
gadolinium (Gd)-loaded apoferritin 1:1 adduct at the biotinylated target sites. The remarkable relaxation
enhancement ability of the Gd-loaded apoferritin system allowed the visualisation of tumour endothelial cells both
in vitro and in vivo when organised in microvessels connected to the mouse vasculature.
Unfortunately, attempts to increase the relaxivity per particle failed, as the preparation method used does not
allow the inclusion of more than 8
10 Gd-HPDO3A molecules per apoferritin cavity. The task of internalizing
a much greater number of paramagnetic centres inside the apoferritin cavity has been pursued by dissolving the
solid
b
-MnOOH phase that one may create by exposing the protein to a concentrated solution of Mn(II) salts at
