Noninvasive imaging of pancreatic inflammation and its reversal in type 1 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.
Turvey
Stuart E
SE
Section on Immunology and Immunogenetics, Joslin Diabetes Center, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
Swart
Eric
E
Denis
Maria C
MC
Mahmood
Umar
U
Benoist
Christophe
C
Weissleder
Ralph
R
Mathis
Diane
D
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D003520:Cyclophosphamide / Q000633:toxicity; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D049329:Nanostructures; D010179:Pancreas / Q000166:cytology / Q000276:immunology / Q000473:pathology
D017252:CD3 Complex; D007074:Immunoglobulin G; D003520:Cyclophosphamide