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in vivo by MRI of athymic (nu/nu) mice bearing xenografts (this is a widely used
and well-established animal model which mimics natural gliomas) [101, 102].
Nanoparticle internalization by glioma cells was visualized using TEM, and quanti-
fi ed by measuring the intracellular iron content using colorimetry. In vitro MR
phantom imaging and in vivo small-animal MRI demonstrated the targeting ability
of the nanoprobes in tumor cells. In addition, the R 2 relaxation rates were mea-
sured to quantify the degree of contrast enhancement.
The specifi city of the nanoprobes was evaluated by comparing the contrast
enhancement between the tumor and normal tissue regions of mice. NP- PEG - CTX
and NP-PEG-succinimidyl iodoacetate (SIA) were administered at the same con-
centration, after which each of the mice were imaged prior to, and at various time
points after, an intravenous injection of the nanoprobes (at a dosage of 6 mg Fe kg −1 ).
Figures 6.2a and b show the anatomical images of coronal and sagittal planes used
to determine the tumor position along the fl ank of the animal. Multi-spin-echo
pulse sequences were utilized to obtain a series of images over a range of echo
times (TEs) for the tumor regions of axial cross-sectional. The targeting ability of
the NP- PEG - CTX (Figure 6.2 d), in comparison to NP - PEG - SIA (Figure 6.2 c), was
evident in MR images acquired in the tumor at 3 h post-injection in mice.
(a)
(b)
Sagittal
(c)
(d)
8
6
4
2
0
Coronal
NP-PEG-SIA
NP-PEG-CTX
Axial
Figure 6.2 MRI anatomical image of a mouse
in (a) the coronal plane. The dotted line
shows the approximate location of the axial
cross-sections displayed in panels (c) and (d);
(b) Anatomical image in the sagittal plane.
This displays the location of the 9L xenograft
tumor; (c, d) Changes in R2 relaxivity values
for the tumor regions (superimposed over
anatomical MR images) for mice receiving
(c) nontargeting NP - PEG - SIA and
(d) NP - PEG - CTX at 3 h post injection. The
arrow in (b) marks the tumor location. These
are representative images from three
independent experiments with similar results.
Reprinted with permission from Ref. [95].
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