Biology Reference
In-Depth Information
isotopes such as technetium-99m pertechnetate (
99m
TcO
4
−
), rhenium-188
perrhenate and iodine
[108]
. The
99m
TcO
4
−
-labeled Treg appeared pheno-
typically normal (i.e. positive for CD4, CD25 and FoxP3), was viable and
was able to suppress T cells in an
in vitro
suppression assay. SPECT imag-
ing detected that within 24 hours of injection, Tregs were observed in the
spleen, which was confirmed via FACS analysis. This study indicated that
SPECT-CT technology could be an effective strategy for imaging Treg in var-
ious models of adoptive cellular therapy.
Magnetic resonance imaging
Magnetic resonance imaging (MRI) has developed into one of the most
powerful high-resolution imaging tools in the biomedical sciences. MRI
is based on the detection of unpaired nuclear spins (e.g. hydrogen nuclei
of water) which become aligned when placed into a magnetic field; the
aligned fields then produce a rotating magnetic field, which generates weak
radio waves that are detectable by a scanner
[108]
. Interactions between
protons or other nuclei as well as between nuclei and their surrounding
molecules in a tissue of interest cause the nuclei to spin (resonate) at differ-
ent frequencies
[109]
. This results in exceptional spatial resolution which is
at least one order of magnitude higher than is found with nuclear or optical
imaging. MRI has been applied to the study of oxygenation, tissue elastic-
ity, neuronal function, metabolism, and detection of molecular probes and
labeled cells, making it a very useful and versatile technology.
73
The most well-known application of MRI is structural imaging. MR micros-
copy at high field strengths, such as 7 or 9.4 Tesla, can produce high signal-
to-noise 3D data sets with spatial resolutions of approximately 40 μm down
to even micron-level resolution
[110,111]
. An exciting development over
the past decade is the technology to label cells with ferumoxides or super-
paramagnetic iron oxide (SPIO) nanoparticles to track their migration
[112]
.
This enables the detection of the cells within the high-resolution spatial MR
image. Thus structural, physiological and other information is in the same
image space as the cells of interest. This greatly reduces the complexity and
potential for error by gaining similar information through the use of multi-
modal imaging technologies (e.g. BLI + CT, or PET + MRI).
MRI imaging of immune cells
In an early study, Kircher et al. labeled antigen-specific CD8
+
T cells with
cross-linked iron oxide (CLIO) nanoparticles, and followed their
in vivo
trafficking in a tumor model
[113]
. Previous labeling methods were not very
effective due to huge dilutions of administered cells and usually involved
a local injection of cells. In this study, however, the labeling with CLIO
nanoparticles allowed a detection threshold of OVA-specific CD8
+
T cells
of approximately 3 cells/voxel in live mice. The labeling procedure did not
affect the killing ability of the CD8
+
T cells
in vitro
, nor did it affect rate of
attachment, rolling fraction, stable arrest or transmigration in murine heart
endothelium under
in vitro
flow conditions. By culturing the CD8
+
T cells
with antigen-loaded APCs
in vitro
, CLIO labels could be maintained for over
120 hours. By imaging OVA-containing tumors in three dimensions across
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