In vivo imaging of islet transplantation

Type 1 diabetes mellitus is characterized by the selective destruction of insulin-producing beta cells, which leads to a deficiency in insulin secretion and, as a result, to hyperglycemia. At present, transplantation of pancreatic islets is an emerging and promising clinical modality, which can render individuals with type 1 diabetes insulin independent without increasing the incidence of hypoglycemic events. To monitor transplantation efficiency and graft survival, reliable noninvasive imaging methods are needed. If such methods were introduced into the clinic, essential information could be obtained repeatedly and noninvasively. Here we report on the in vivo detection of transplanted human pancreatic islets using magnetic resonance imaging (MRI) that allowed noninvasive monitoring of islet grafts in diabetic mice in real time. We anticipate that the information obtained in this study would ultimately result in the ability to detect and monitor islet engraftment in humans, which would greatly aid the clinical management of this disease.

[1]  S. Bonner-Weir,et al.  Vulnerability of Islets in the Immediate Posttransplantation Period: Dynamic Changes in Structure and Function , 1996, Diabetes.

[2]  R. Weissleder,et al.  Uptake of dextran‐coated monocrystalline iron oxides in tumor cells and macrophages , 1997, Journal of magnetic resonance imaging : JMRI.

[3]  R Weissleder,et al.  High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. , 1999, Bioconjugate chemistry.

[4]  J A Frank,et al.  Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Ralph Weissleder,et al.  Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells , 2000, Nature Biotechnology.

[6]  E. Ryan,et al.  Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. , 2000, The New England journal of medicine.

[7]  W. Malaisse,et al.  Assessment of islet beta-cell mass in isolated rat pancreases perfused with D-[(3)H]mannoheptulose. , 2001, American journal of physiology. Endocrinology and metabolism.

[8]  R. Weissleder,et al.  Noninvasive In Vivo Measurement of β-Cell Mass in Mouse Model of Diabetes , 2001 .

[9]  W. Malaisse,et al.  Assessment of B-cell mass in isolated islets exposed to D-[3H]mannoheptulose. , 2001, International journal of molecular medicine.

[10]  W. Malaisse,et al.  Assessment of islet β-cell mass in isolated rat pancreases perfused with d-[3H]mannoheptulose , 2001 .

[11]  Peter van Gelderen,et al.  Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells , 2001, Nature Biotechnology.

[12]  R. Weissleder,et al.  MRI of insulitis in autoimmune diabetes , 2002, Magnetic resonance in medicine.

[13]  Jeff W M Bulte,et al.  In Vivo Magnetic Resonance Tracking of Magnetically Labeled Cells after Transplantation , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  C. Ricordi,et al.  Edmonton's islet success has indeed been replicated elsewhere , 2003, The Lancet.

[15]  S. Gambhir,et al.  Molecular imaging in living subjects: seeing fundamental biological processes in a new light. , 2003, Genes & development.

[16]  Heather Kalish,et al.  Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. , 2003, Radiology.

[17]  Activated macrophages require T cells for xenograft rejection under the kidney capsule. , 2003, Immunology and cell biology.

[18]  Peter Girman,et al.  MRI of transplanted pancreatic islets , 2004, Magnetic resonance in medicine.

[19]  Heather Kalish,et al.  Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. , 2004, Blood.

[20]  Sanjiv Sam Gambhir,et al.  Bioluminescent monitoring of islet graft survival after transplantation. , 2004, Molecular therapy : the journal of the American Society of Gene Therapy.

[21]  A. Alavi,et al.  Synthesis and evaluation of fluorine-18 labeled glyburide analogs as beta-cell imaging agents. , 2004, Nuclear medicine and biology.

[22]  A. Moore,et al.  Tracking the recruitment of diabetogenic CD8+ T-cells to the pancreas in real time. , 2004, Diabetes.

[23]  Blue Cross Islet Transplantation in Patients with Type 1 Diabetes Mellitus , 2004 .

[24]  Anna Moore,et al.  In Vivo Targeting of Underglycosylated MUC-1 Tumor Antigen Using a Multimodal Imaging Probe , 2004, Cancer Research.

[25]  D. Harlan,et al.  Assessment of Pancreatic Islet Mass after Islet Transplantation Using In Vivo Bioluminescence Imaging , 2005, Transplantation.