New Imaging Technology at Joslin Shown to Detect Early Signs of Type 1 Diabetes in Animal Models.

BOSTON -- By the time overt symptoms of type 1 diabetes appear in an individual, destruction of the insulin-producing beta cells of the pancreas has already progressed significantly. However, findings by researchers at Joslin Diabetes Center and Massachusetts General Hospital, published in the Aug. 24 issue of Proceedings of the National Academy of Sciences, show that a powerful new imaging technology gives scientists a glimpse into the earliest stages of the inflammatory process leading to type 1 diabetes in laboratory animals. The new findings one day may be useful for predicting whether and when diabetes will develop in humans.

Type 1 diabetes is an autoimmune disease in which the body's immune system mistakenly launches an attack on the insulin-producing beta cells of the pancreatic islets. This process may eventually destroy the beta cells, preventing them from producing sufficient insulin, so that high blood-glucose levels--and full-blown diabetes--develop. Early in this process, white blood cells called T-cells invade the islets (an inflammatory condition known as "insulitis"). A very early marker of this inflammation is increased permeability (leaking) of the tiny blood vessels surrounding and within the islets.

Until recently, the only way to track type 1 diabetes in its earliest stages was to measure blood levels of autoantibodies (the immune system's "guided missiles") directed against pancreatic islet proteins. Yet, these tests are only an indirect indication of the disease process, and don't allow researchers to directly follow the progression of disease.

This gap may someday be filled by a new technology that exploits magnetic resonance imaging, commonly known as MRI, to monitor miniscule magnetic nanoparticles leaking from the blood vessels of the pancreas, according to Maria Denis, Ph.D., Christophe Benoist, M.D., Ph.D., and Diane Mathis, Ph.D., of Joslin Diabetes Center, and Umar Mahmood, M.D., Ph.D., and Ralph Weissleder, M.D., Ph.D., of Massachusetts General Hospital, both in Boston. Dr. Denis, a former Joslin research fellow, now works at the BSRC Alexander Fleming Institute of Immunology in Greece. The Joslin and MGH researchers demonstrated the effectiveness of using this new imaging technology to detect the earliest stages of type 1 diabetes in a mouse model.

How the technology works

The new imaging technology uses tiny probes called long-circulating magnetofluorescent nanoparticles (CMFN). These particles contain magnetic nanocrystals of iron oxide, which are very easily detected by MRI. After being injected intravenously, CMFN travels throughout the body, including through the tiny blood vessels of the pancreas. If these vessels have started to become permeable as a result of islet inflammation, more CMFN tends to leak out and collect in the surrounding tissue, as can be seen on the MRI. This technique allows researchers to observe this early inflammatory process over time. "Thus, we have the means to non-invasively monitor the initiation and progression of insulitis in mouse models of type 1 diabetes in vivo and in real time," Dr. Mathis comments.

The researchers say that this new imaging process may prove an invaluable aid in helping researchers and clinicians to spot early insulitis and to monitor how it changes, during the development of disease and after experimental or therapeutic interventions aimed at stopping its progression. Further, they point out that the technique already has been used safely and effectively by the MGH group in human clinical trials to detect the spread of prostate cancer to the lymph nodes. "Given the known safety of magnetic nanoparticles in humans, the technology might someday be used in individuals who are genetically at risk for diabetes to detect this autoimmune process in its earliest stages," Dr. Benoist suggests.

Drs. Mathis and Benoist hold the William T. Young Chair in Diabetes Research at Joslin and co-head the Section on Immunology and Immunogenetics. Both are Professors of Medicine at Harvard Medical School. Dr. Weissleder is Professor of Radiology at Harvard Medical School and the Director of the Center for Molecular Imaging Research at MGH. This research was funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

For more information on Joslin, call 1-800-JOSLIN-1 or visit www.joslin.org.