Imaging in Stem Cell Transplant and Cell-based Therapy

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Clio-tat peptides [ 41 ] or magnetic relaxation switches [ 42 ] have the ability to track the
distribution and differentiation of progenitor and stem cells by high-resolution in vivo
imaging techniques having significant clinical and research implications.


8.4.2 Direct Labeling of Cells Using Radionuclides


Direct labeling with radionuclides like Indium (In)-111 provides lot of valuable
information in stem cell homing. Current data suggests that a small number of
cells ultimately home to injured myocardium while a significant proportion of
cells accumulate in other organs like lungs, this at the same time corroborates with
high sensitivity of nuclear imaging technique [ 43 , 44 ]. Homing of In-111–labeled
stem cells to infarcted myocardium has been successfully visualized using imag-
ing techniques like single-photon emission computed tomography (SPECT)-CT
[ 39 ]. Other modalities like 18F-FDG and 3D PET scanning have been used follow-
ing therapeutic application of intracoronary autologous bone marrow cell (BMCs)
transplantation in patients with acute myocardial infarction. Following site directed
and systemic administration the unselected BMCs labeled with 18F-FDG can be
detected in the infarcted myocardium while the remaining activity can be found
other organs like liver and spleen [ 21 ]. Unfortunately, because of the short half-life
of^18 F-fluorodeoxyglucose, other isotopes with a longer half-life may need to be
evaluated for optimal long-term tracking of stem cells. Also, use of intravenous
route causes lesser degree of engrafting of stem cells as compared to site directed
delivery of stem cells. It is well known that early infusion results in significantly
higher uptake in the heart [ 29 ]. Accumulation of injected stem cells can be seen
within hours after intracoronary infusion and outside of the myocardium higher
stem cell accumulation is seen in spleen, liver, bladder and bone marrow. The
delayed images on PET scan show a prolonged residence of stem cells at the myo-
cardium [ 29 ]. Use of agents like technetium (Tc)-99m exametazime (HMPAO) has
demonstrated the dynamic nature of cardiac cell engraftment after trans coronary
transplantation in patients with acute myocardial infarction [ 45 ]. In comparison to
MRI, radionuclide techniques have the advantage of a lower background signal
and higher sensitivity at the cost of lower spatial resolution.


8.4.3 Reporter Genes for Cardiovascular Cell Imaging


Imaging reporter gene expression is a useful technique for noninvasive monitoring
of gene therapy [ 46 ]. These reporter genes can be transferred to cells for genetic
labeling prior to in vivo administration. These can later be detected by radio-labeled
or optical reporter probes specific for the reporter gene within the transduced cell.
Use of reporter gene labeling is more specific and requires the expression of the
reporter gene and activity of the reporter-gene product which in turn depends on
viability of therapeutic cells [ 47 ].


S. Raina et al.
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