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  • New MRI Technique Can Detect Diabetes

    A major stumbling block for research on and treatment of type 1 diabetes is the inability to directly, but noninvasively, visualize the lymphocytic/inflammatory lesions in the pancreatic islets. One potential approach to surmounting this impediment is to exploit MRI of magnetic nanoparticles (MNP) to visualize changes in the microvasculature that invariably accompany inflammation. MNP-MRI did indeed detect vascular leakage in association with insulitis in murine models of type 1 diabetes, permitting noninvasive visualization of the inflammatory lesions in vivo in real time. We demonstrate, in proof-of-principle experiments, that this strategy allows one to predict, within 3 days of completing treatment with an anti-CD3 monoclonal antibody, which NOD mice with recent-onset diabetes are responding to therapy and may eventually be cured. Importantly, an essentially identical MNP-MRI strategy has previously been used with great success to image lymph node metastases in prostate cancer patients. This success strongly argues for rapid translation of these preclinical observations to prediction and/or stratification of type 1 diabetes and treatment of individuals with the disease; this would provide a crucially needed early predictor of response to therapy.

    Type 1 diabetes is an autoimmune disease characterized by lymphocytic infiltration of the pancreatic islets, culminating in specific destruction of insulin-producing ? cells (1–3). This immunological process unfolds over a variable number of years, resulting in clinically detectable hyperglycemia and, ultimately, diagnosis of diabetes. At the present time, the islet infiltrate, termed insulitis, is only detectable by biopsy (4), usually at autopsy. The ability to detect lymphocytic infiltration and associated inflammation of the pancreas through noninvasive means would most likely have clinical benefits in 2 major areas. The first is diagnostic: helping physicians distinguish patients that have an a typical type 1 rather than type 2 diabetes or identifying individuals with preclinical type 1 diabetes as early as possible, ensuring early initiation of therapy and regular follow-up. The second area, of perhaps even greater potential, involves following patients who are under-going interventions to prevent or reverse overt disease. Currently, the only accepted endpoint for trials in these areas is the clinical diagnosis of diabetes. This makes the trials lengthy and expensive — for example, 7 years for the parenteral insulin treatment arm of the Diabetes Prevention Trial–Type 1 (5). An accurate method for noninvasively following the progression or regression of insulitis might permit the early recognition and monitoring of potentially beneficial therapies and the discarding of ineffective treatments.The complex cellular infiltrate associated with autoimmune diabetes is accompanied by a range of alterations in the micro vasculature, including modification of endothelial cells, vascular swelling, increased islet blood flow, and edema (6–13). These microvascular changes may be amenable to visualization with a range of newly described imaging probes and techniques (14). A particularly attractive approach is the use of high spatial resolution MRI combined with magnetic nanoparticles (MNP) in deriving physiologic (15) and molecular (16) information. One highly useful MNP platform has been the application of long-circulating, dextran-coated, monocrystalline, superparamagnetic iron oxides that exhibit strong magnetic behavior detectable by high-resolution MRI. The attractiveness of this approach is heightened by our recent experiments demonstrating that it can be used to identify insulitis in the BDC2.5 TCR Tg mouse model of type 1 diabetes (17) coupled with its demonstrated safety and utility in the visualization of small and otherwise undetectable lymph node metasta-ses in patients with prostate cancer (18).

    Source: Journal of Clinical Investigation

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