BADERC-Anna Moore

Anna Moore, Ph.D.

Non-invasive Imaging Pancreatic beta-cells

Non-invasive imaging of a diabetic pancreas is a long sought goal of clinical investigators. Challenges remain in imaging the diabetic pancreas remain and the studies on pancreatic tissues are generally limited to autopsy. The main reasons for that are: a) the islets of Langerhans represent only 2-3% of pancreatic tissue, b) the pancreas is not easily accessible for biopsy thus excluding histological approaches and 3) due to the small size of the islets and the chronicity of some diabetes conditions (for example, chronic insulitis) conventional CT, NMR and ultrasound techniques have a very low sensitivity. This presentation will focus on the new, fast developing field of molecular imaging of diabetic conditions both in Type I and Type II diabetes. The major areas under study include imaging of beta-cell mass (BCM), early detection of lymphocyte infiltration in pancreatic islets during autoimmune attack, imaging of beta-cell apoptosis, imaging of pancreatic islet vasculature, imaging of islet transplantation and others.

A variety of molecular imaging modalities have been previously used primarily to study neoplastic transformation. Here we utilized these methods including magnetic resonance imaging (MRI), nuclear and optical imaging to study diabetic pancreas. In spite of being only a few years old, this new field has shown significant progress in developing methods to study BCM, lymphocyte invasion, islet vasculature and imaging of transplanted islets. The results of these and other ongoing studies will be ultimately used for devising interventions for diabetic patients, monitoring their efficacy, as well as imaging high-risk patients. We expect that these methods will give us the ability to detect and, possibly, follow the early progression of diabetes, which will greatly aid and simplify the pharmacological intervention of this disease. It would also help in difficult disease diagnoses (type 1B diabetics, Late Autoimmune Diabetes of Adults, LADA), monitoring disease course and evaluating the effect of immunointervention and transplantation.

References

Moore A, Grimm J, Han B, Santamaria P. Tracking the recruitment of diabetogenic CD8+ T cells to the pancreas in real time. Diabetes, 2004, 53:1459-1466.
Medarova Z, Bonner-Weir S, Lipes M, Moore A. Imaging b-cell death with a near-infrared probe. Diabetes, 2005, 54: 1780-1788.
Evgenov N, Medarova Z, Dai G, Bonner-Weir S, Moore A. In vivo imaging of islet transplantation. Nature Med, 2006, 12:144-148.
Medarova Z, Evgenov N, Dai G, Bonner-Weir S, Moore A. In vivo multimodal imaging of transplanted pancreatic islets. Nature Prot, 2006, 1:428-434.
Evgenov N, Medarova Z, Pratt J, Pantazopoulos P, Leyting S, Bonner-Weir S, Moore A. In vivo imaging of immune rejection in transplanted pancreatic islets. Diabetes, 2006, 55:2419-2428.
Medarova Z, Castillo G, Dai G, Bolotin E, Bogdanov A, Moore A. Non-invasive magnetic resonance imaging of microvascular changes in Type 1 diabetes, Diabetes, 2007, 56:2677-2682.
Ran C, Pantazopoulos P, Medarova Z, Moore A. Synthesis and testing of beta-cell specific streptozotocin-derived near infrared imaging probes, Angew Chem, 2007, 46-47:8998-9001.
Medarova Z, Tsai S, Evgenov N, Santamaria P, Moore A. In vivo imaging of a diabetogenic CD8+ T cell response during type 1 diabetes progression, Magn Reson Med, 2008, 59:712-720.
Evgenov N, Pratt J, Pantazopoulos P, Moore A. Effects of Glucose Toxicity and Islet Purity on In Vivo MR Imaging of Transplanted Pancreatic Islets, Transplantation, 2008, 85:1091-1098.
Medarova Z, Kumar, M, Ng, SW, Junzheng, Y, Barteneva N, Evgenov N, Petkova V, Moore A. Multifunctional magnetic nanocarriers for image-tagged siRNA delivery to intact pancreatic islets. Transplantation, 2008 86:1170-1177.
Moore A. Advances in beta-cell imaging, Eur J Radiol, 2009, 70:254-257.
Medarova Z, Vallabhajosyula P, Tena A, Evgenov N, Pantazopoulos P, Tchipashvili V, Weir G, Sachs D, Moore A. In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates. Transplantation, 2009, 87(11): in press.






			Anna Moore, Ph.D. Non-invasive Imaging Pancreatic beta-cells Non-invasive imaging of a diabetic pancreas is a long sought goal of clinical investigators. Challenges remain in imaging the diabetic pancreas remain and the studies on pancreatic tissues are generally limited to autopsy. The main reasons for that are: a) the islets of Langerhans represent only 2-3% of pancreatic tissue, b) the pancreas is not easily accessible for biopsy thus excluding histological approaches and 3) due to the small size of the islets and the chronicity of some diabetes conditions (for example, chronic insulitis) conventional CT, NMR and ultrasound techniques have a very low sensitivity. This presentation will focus on the new, fast developing field of molecular imaging of diabetic conditions both in Type I and Type II diabetes. The major areas under study include imaging of beta-cell mass (BCM), early detection of lymphocyte infiltration in pancreatic islets during autoimmune attack, imaging of beta-cell apoptosis, imaging of pancreatic islet vasculature, imaging of islet transplantation and others. A variety of molecular imaging modalities have been previously used primarily to study neoplastic transformation. Here we utilized these methods including magnetic resonance imaging (MRI), nuclear and optical imaging to study diabetic pancreas. In spite of being only a few years old, this new field has shown significant progress in developing methods to study BCM, lymphocyte invasion, islet vasculature and imaging of transplanted islets. The results of these and other ongoing studies will be ultimately used for devising interventions for diabetic patients, monitoring their efficacy, as well as imaging high-risk patients. We expect that these methods will give us the ability to detect and, possibly, follow the early progression of diabetes, which will greatly aid and simplify the pharmacological intervention of this disease. It would also help in difficult disease diagnoses (type 1B diabetics, Late Autoimmune Diabetes of Adults, LADA), monitoring disease course and evaluating the effect of immunointervention and transplantation. References Moore A, Grimm J, Han B, Santamaria P. Tracking the recruitment of diabetogenic CD8+ T cells to the pancreas in real time. Diabetes, 2004, 53:1459-1466. Medarova Z, Bonner-Weir S, Lipes M, Moore A. Imaging b-cell death with a near-infrared probe. Diabetes, 2005, 54: 1780-1788. Evgenov N, Medarova Z, Dai G, Bonner-Weir S, Moore A. In vivo imaging of islet transplantation. Nature Med, 2006, 12:144-148. Medarova Z, Evgenov N, Dai G, Bonner-Weir S, Moore A. In vivo multimodal imaging of transplanted pancreatic islets. Nature Prot, 2006, 1:428-434. Evgenov N, Medarova Z, Pratt J, Pantazopoulos P, Leyting S, Bonner-Weir S, Moore A. In vivo imaging of immune rejection in transplanted pancreatic islets. Diabetes, 2006, 55:2419-2428. Medarova Z, Castillo G, Dai G, Bolotin E, Bogdanov A, Moore A. Non-invasive magnetic resonance imaging of microvascular changes in Type 1 diabetes, Diabetes, 2007, 56:2677-2682. Ran C, Pantazopoulos P, Medarova Z, Moore A. Synthesis and testing of beta-cell specific streptozotocin-derived near infrared imaging probes, Angew Chem, 2007, 46-47:8998-9001. Medarova Z, Tsai S, Evgenov N, Santamaria P, Moore A. In vivo imaging of a diabetogenic CD8+ T cell response during type 1 diabetes progression, Magn Reson Med, 2008, 59:712-720. Evgenov N, Pratt J, Pantazopoulos P, Moore A. Effects of Glucose Toxicity and Islet Purity on In Vivo MR Imaging of Transplanted Pancreatic Islets, Transplantation, 2008, 85:1091-1098. Medarova Z, Kumar, M, Ng, SW, Junzheng, Y, Barteneva N, Evgenov N, Petkova V, Moore A. Multifunctional magnetic nanocarriers for image-tagged siRNA delivery to intact pancreatic islets. Transplantation, 2008 86:1170-1177. Moore A. Advances in beta-cell imaging, Eur J Radiol, 2009, 70:254-257. Medarova Z, Vallabhajosyula P, Tena A, Evgenov N, Pantazopoulos P, Tchipashvili V, Weir G, Sachs D, Moore A. In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates. Transplantation, 2009, 87(11): in press.