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MRI can track survival of pancreatic
islets after transplantation
Noninvasive monitoring could reveal
complex factors behind islet loss, improve outcomes
BOSTON - September 12, 2006 - Magnetic resonance imaging
(MRI) with an approved contrast agent may provide a practical way
of monitoring the survival of transplanted pancreatic islets. In
the September issue of the journal Diabetes, researchers
from the Martinos
Center for Biomedical Imaging at Massachusetts General Hospital
(MGH) report successfully tracking over time the fate of islets
transplanted into mice using a protocol currently being tested in
human patients.
"Clinical trials and animal studies show that there is a significant
loss of islets following transplantation due to many factors, not
just rejection," says Anna Moore, PhD, of the MGH Martinos
Center, who led the study. "Currently there is no direct way
to follow the causes behind this loss and how it proceeds over time.
Monitoring islet survival by noninvasive imaging could give us the
ability to detect and measure rates of islet loss under a variety
of conditions, which could help develop procedures leading to better
therapeutic outcomes."
Pancreatic islet transplants are being investigated as a way to
treat or cure patients with type 1 diabetes, in which the insulin-producing
islets are attacked by the body's immune system. In an effort to
replace destroyed islets and restore normal insulin production and
glucose metabolism, several methods of islet transplantation have
been developed and tested. One of the most promising - called the
Edmonton Protocol, since it was developed at the University of Alberta
- is currently the subject of a multicenter clinical trial. In a
2005 report, the Edmonton group noted that, while islet survival
is improving, problems continue to exist both with immune rejection
and with the initial post-transplantation engraftment of islets.
Even in animal studies involving transplants from genetically identical
donors, which should not produce immune rejection, as many as 60
percent of islets are lost in soon after the procedure.
In a previously published animal study, the MGH-Martinos group showed
that MRI could detect transplanted islets that had been marked with
experimental iron-containing nanoparticles. The current study utilized
islets labeled with Feridex, an FDA-approved contrast agent, and
procedures virtually identical to the Edmonton protocol, in which
islets are infused into the recipient's liver. Labeled islets were
transplanted into mice with a normal immune system and into mice
with a severe genetic immune deficiency that would practically eliminate
the rejection process. MR images of the animals' livers were taken
seven times over the 14 days after the transplant procedure.
The results verified that that MRI could track the labeled islets
over time and reveal how many were surviving. For both groups of
mice, the number of islets began to drop immediately after transplantation
and reached a plateau at 10 to 14 days. The researchers note that
much of the early islet death probably was caused by factors other
than rejection, such as damage during the transplant procedure.
However, by day 10 the mice with normal immune systems showed a
20 percent greater loss of islets than did the immune-deficient
animals - probably the result of rejection - and close examination
verified significant immune cell activity in the normal mice.
"Since MRI can provide comprehensive information about the
presence and position within the body of entities as small as islets
and can be performed repeatedly without subjecting patients to radiation
or any invasive procedure, we think it is the most appropriate imaging
modality to monitor islet survival," says Moore. "Feridex
is an approved imaging agent, so the next logical step could be
human clinical trials, although it may be helpful to work on improving
the imaging procedures with larger animals first." Moore is
an assistant professor of Radiology at Harvard Medical School and
director of the Molecular Imaging Laboratory at the Martinos Center.
Co-authors of the Diabetes report are first author Natalia
Evgenov, MD, Zdravka Medarova, PhD, John Pratt, PhD, Pamela Pantazopoulos,
and Simone Leyting of the Martinos Center at MGH, and Susan Bonner-Weir,
PhD, Joslin Diabetes Center. The research was supported by grants
from the National Institutes of Health.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, transplantation biology and photomedicine. MGH and Brigham
and Women's Hospital are founding members of Partners HealthCare
HealthCare System, a Boston-based integrated health care delivery
system.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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