title: Noninvasive imaging of pancreatic inflammation and its reversal in type 1 diabetes.
abstract: 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.
authors.affiliation: Section on Immunology and Immunogenetics, Joslin Diabetes Center, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Turvey
authors.forename: Eric
authors.initials: E
authors.lastname: Swart
authors.forename: Maria C
authors.initials: MC
authors.lastname: Denis
authors.forename: Umar
authors.initials: U
authors.lastname: Mahmood
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
mesh_terms: 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
chemical_list: D017252:CD3 Complex; D007074:Immunoglobulin G; D003520:Cyclophosphamide