Abstract
To explore the possibility to use 1.5 T MRI in imaging of accumulating gadolinium (Gd) into inflamed en- docrine pancreas (insulitis), we compared intravenously delivered IL-2-Gd-DTPA and Gd-DTPA (Magne- vist®) in phenotypically healthy 12 weeks old female non-obese diabetic (NOD) mice. At 1 to 48 h after the injection mice were sacrificed and the pancreas-to-background ratio was determined using MRI. In addition Gd concentration of the pancreas and plasma were measured. The pancreas-to-plasma ratio of Gd was 25-fold 24 h after the i.v. injection of IL-2-Gd-DTPA. At the same time the pancreas-to-background ratio measured with 1.5T MRI was 1.5-times higher in the NOD mice receiving IL-2-Gd-DTPA than Magnevist® (271 ± 37 vs. 183 ± 0,1, P = 0.04) indicating that sufficient differences may exist between IL-2-Gd-DTPA accumulating in the pancreas and in the surrounding tissues to support the use of MRI for imaging of pan- creatic insulitis.
Highlights
Due to the restricted accessibility of the pancreas, direct analysis of events in the islets of Langerhans that precede development of autoimmune diabetes has been problematic
At the same time the pancreas-to-background ratio measured with 1.5T Magnetic resonance imaging (MRI) was 1.5-times higher in the non-obese diabetic (NOD) mice receiving Interleukin 2 (IL-2)-gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) than Magnevist® (271 ± 37 vs. 183 ± 0,1, P = 0.04) indicating that sufficient differences may exist between IL-2-Gd-DTPA accumulating in the pancreas and in the surrounding tissues to support the use of MRI for imaging of pancreatic insulitis
Our preliminary data indicate that IL-2-Gd-DTPA exhibits different pharmacokinetics than Gd-DTPA alone when injected i.v. into 12-week-old NOD mice
Summary
Due to the restricted accessibility of the pancreas, direct analysis of events in the islets of Langerhans that precede development of autoimmune diabetes has been problematic. Methods of in vivo imaging of insulitis might increase understanding of the events that are necessary for the progression toward overt diabetes and help in defining potential molecular targets for prevention of autoimmunity and type 1 diabetes. Development of insulitis, characterized by accumulation of lymphocytes in and around the islets of Langerhans [2,3], is a prerequisite for autoimmune destruction of the beta cells and may in man precede clinical symptoms of insulin deficiency by months or years. Clinical diabetes in man is believed to develop when 80% - 90% of the insulin producing beta cells have been destroyed [4]. Insulitis in NOD mice begins at the age of 3 to 5 weeks, its extent gradually increases until the age of 16 to 20 weeks [5], and by the age of 30 weeks, the cumulative incidence of diabetes reaches 60% - 90% in female NOD mice [6]
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