title: Immune rejection after pancreatic islet cell transplantation: in vivo dual contrast-enhanced MR imaging in a mouse model.
abstract: OBJECTIVE
  To detect adoptively transferred immune attack in a mouse model of islet cell transplantation by using a long-circulating paramagnetic T1 contrast agent, a protected graft copolymer (PGC) that is covalently linked to gadolinium-diethylenetriaminepentaacetic acid with fluorescein isothiocyanate (Gd-DTPA-F), which accumulates in the sites of inflammation that are characterized by vascular disruption.
  
  
  METHODS
  All animal experiments were performed in compliance with institutional guidelines and approved by the subcommittee on research animal care. Six nonobese diabetic severe combined immunodeficiency mice received transplanted human islet cells under the kidney capsule and adoptively transferred 5 × 10(6) splenocytes from 6-week-old nonobese diabetic mice. These mice also served as control subjects for comparison of pre- and postadoptive transfer MR imaging results. Mice that received phosphate-buffered saline solution only were included as nonadoptive-transfer control subjects (n = 2). In vivo magnetic resonance (MR) imaging was performed before and 17 hours after intravenous injections of PGC-Gd-DTPA-F, followed by histologic examination. Statistical differences were analyzed by means of a paired Student t test and repeated two-way analysis of variance.
  
  
  RESULTS
  MR imaging results showed significantly greater accumulation of PGC-Gd-DTPA-F in the graft area after immune attack initiated by adoptive transfer of splenocytes compared with that of the same area before the transfer (T1, 137.2 msec ± 39.3 and 239.5 msec ± 17.6, respectively; P < .001). These results were confirmed at histologic examination, which showed considerable leakage of the contrast agent into the islet cell interstitium.
  
  
  CONCLUSIONS
  PGC-Gd-DTPA-F-enhanced MR imaging allows for the in vivo assessment of vascular damage of the graft T cell challenge.
authors.affiliation: Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Building 75, 149 13th St, Charlestown, MA 02129, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Christian
authors.initials: C
authors.lastname: Schuetz
authors.forename: Alana
authors.initials: A
authors.lastname: Ross
authors.forename: Guangping
authors.initials: G
authors.lastname: Dai
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
authors.forename: Anna
authors.initials: A
authors.lastname: Moore
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003287:Contrast Media / Q000008:administration & dosage; D003911:Dextrans / Q000008:administration & dosage; D003920:Diabetes Mellitus / Q000473:pathology / Q000601:surgery; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019786:Gadolinium DTPA / Q000008:administration & dosage; D006084:Graft Rejection / Q000209:etiology* / Q000473:pathology*; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D019786:Gadolinium DTPA