Biomedical Engineering Reference
In-Depth Information
The iron oxide contrast in MRI depends on the size and cellular clustering of nanoparticles.
The SPIOs are typically used as negative T2 contrast, but it has been shown that USPIOs also
produce a more desirable positive T1 contrast [40]. Scaling up production of the extremely
small-sized iron oxide nanoparticles (ESION) and providing positive T1 contrast may enhance
the application of iron oxide for cellular imaging [41].
Another application for iron oxide nanoparticles that takes advantage of their strong
magnetic characteristics is directing the movement of labeled cells after transplantation. An
external magnetic field applied focally can guide cells to the target organ/structure, facilitating
stem-cell trafficking to the desired sites [42-44].
Gadolinium Nanoparticles
Gadolinium (Gd) chelates are widely used in the clinical arena, due to their strong positive
T1 contrast mechanism, circumventing the problems associated with contrast agents that
produce signal voids, such as obscured images, after the administration of SPIO [45].
Unfortunately, those gadolinium chelates do not yield a positive T1 contrast following uptake
by the cells [46]. The wider application of gadolinium for cell tagging maybe hindered by
problems with the production of water-soluble solutions with satisfactory stability [47]. One
solution to overcome these obstacles has been to integrate the metal-based nanoparticles or
polymer-based scaffolds with gadolinium [48, 49], but the gadolinium chelates still produce a
relatively low signal per molecule. In this context, production of gadolinium oxide nanopar-
ticles has shown to be successful in the tracking of hematopoietic cells [50]. This occurred in
concert with the commercial production of dextran-coated gadolinium oxide nanoparticles -
for example, GadoCELLTrack (BioPAL) - which should generate even more interest in this
method [51]. Auxiliary work to further improve the coatings of gadolinium oxide nanopar-
ticles is progressing, with a choice of variations, including shells made of polyethylene glycol
(PEG) [52] and diethylene glycol (DEG) [53], silica [54], and albumins [55]. An alternative
method consists of capturing gadolinium atoms in cages made of carbon nanotubes [56] or
fullerenes [57]. However, the principal advantage of gadolinium oxide is believed to be the
clearance following the death of labeled cells. It has been shown that free Dex-DOTA-Gd3
+
can clear from the grafted area, in contrast to iron oxide nanoparticles [58]. However, this
also has the disadvantage of releasing free Gd
3+
ions that are known to be very toxic. In this
respect, it may be difficult for Gd-based cell imaging to enter the clinical arena.
Manganese Oxide Nanoparticles
The use of manganese and gadolinium as both being positive T1 contrast agents has been rec-
ognized for some time [59]. However, the neurotoxicity of manganese precluded its initial use in
clinical applications [60-62], and gadolinium became the agent of choice for use in patients [63].
Further investigations have shown that the toxic effect of manganese is highly specific to neu-
rons, without affecting any other cell type [64]. The development of methods that facilitate the
manufacture of manganese oxide nanoparticles, with subsequent coating by a biocompatible
PEG-phospholipid, has rejuvenated the interest in manganese, especially in the context of
stem-cell labeling and imaging [65]. While positive T1 contrast is highly desirable, this formula-
tion of manganese oxide nanoparticles proved to be of inferior sensitivity for stem-cell imaging
compared to iron oxide-based contrast agents [66]. A recent advancement in the manufacture
of a hollow structure of manganese oxide nanoparticles, coated with mesoporous silica, yielded
increased T1 signal through better entrance of water molecules to the magnetic core [67].
