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clinic
[100,101]
. When compared to SPECT, PET is more sensitive (due to
higher energy photons) and versatile, and can be subject to scatter correc-
tion. PET images are, therefore, generally of higher quality. SPECT imaging,
on the other hand, is typically much less expensive (because it does not
require a cyclotron) and can also be used for simultaneous imaging of mul-
tiple radio-nucleotides emitting γ-rays with different energies. Thus, SPECT
could potentially allow simultaneous detection of multiple cell types or bio-
logical events, which is not possible with PET.
Nuclear imaging of GVHD and immune cell trafficking
PET imaging was successfully utilized to assess intestinal GVHD in a
murine model of acute GVHD
[102]
. To induce GVHD, recipient mice were
given myeloablative irradiation, allogeneic bone marrow, and splenocytes.
GVHD was monitored in live mice by weight loss, posture, activity, fur tex-
ture and skin integrity, and confirmed via histology. At 21 days post-trans-
plant,
18
18F-fluorodeoxyglucose (FDG) was injected i.v., and PET imaging
performed 1 hour later. There was a pronounced increase in uptake of FDG
through the colon in mice receiving splenocytes compared with healthy
controls (
Figure 4.1
C). Histological analysis confirmed that the gut inflam-
mation was mainly localized to the colon. Following the PET scans, fluores-
cence microscopy of donor cells expressing eGFP confirmed that there was
a massive infiltration of the colon by CD4
+
and CD8
+
T cells. Thus, FDG-
PET could represent a significant improvement over the standard method
of using histologic analysis of mucosal biopsy specimens retrieved via endos-
copy of the upper and lower intestinal tract
[103]
. This traditional method is
invasive and can present a health risk to patients who are already prone to
thrombocytopenia
[104]
. Additionally, histological scoring of intestinal GVHD
incorporates such features as cellular infiltrates and apoptotic bodies which
are rather non-specific and require context for proper interpretation
[105]
.
72
PET and SPECT can also be used to monitor immune cells by direct
ex vivo
labeling techniques. Direct labeling involves the incubation of a radiolabeled
probe with the cell type of interest before infusion of the cells into recipi-
ent animals for serial imaging. This method was used by Pittet et al. who
employed this approach to image homing of cytolytic T lymphocytes (CTLs)
to tumor sites
[106]
. They visualized
111
In-oxine-labeled hemagglutinin
(HA)-specific CTLs trafficking to tumor sites with a combination SPECT-CT
imaging system. They found that CTLs appeared at tumor sites as quickly
as 2 hours post-infusion and localized primarily to the central region of
HA
+
tumors, but had more diffuse signals in HA
−
tumors. As
111
In-oxine is
FDA-approved for clinical use, this technology may be able to find use to
assess the efficacy of immunization procedures in tumor immunotherapy.
Although direct labeling can be effective, disadvantages of direct labeling are
that the labeling procedure can often be toxic to cells, is not specific to viable
cells, can be lost upon cell death (and taken up by phagocytic cells) and the
label becomes diluted as cells divide
[107]
. To circumvent these issues, PET
and SPECT reporter genes have been developed which can mediate spe-
cific cytosolic accumulation of tracers. In a study by Sharif-Paghaleh et al. it
was demonstrated that CD4
+
CD25
+
Treg could be transduced to express the
reporter gene human Sodium Iodine Symporter (NIS) which incorporates
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