BADERC-Anna Moore

Anna Moore, Ph.D.

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 approaches to the measurement of beta-cell mass (BCM), early detection of lymphocyte infiltration in pancreatic islets during autoimmune attack and methods visualizing beta-cell apoptosis occurring in Type I and Type II diabetes mellitus.

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 and its consequences in animal models. Interest in this field is evident by ongoing studies by other investigators currently focused on imaging of transplanted islets in vivo using bioluminescence imaging.

The results of these and other 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:

1. Moore A, Bonner-Weir S, Weissleder R. Non-invasive in vivo measurement of beta-cell mass in mouse model of diabetes. Diabetes, 2001, 50:2231-2236.

2. Moore A, Zhe P, Cory D, Högemann D, Lipes M, Weissleder R. High resolution imaging of infiltration of immune cells in mouse model of diabetes Type I. Proceedings of the meeting High Resolution Imaging in Small Animals 2001. Rockville, MD, 2001, Session 5, p.110.

3. Moore A, Sun PZ, Cory D, Högemann D, Weissleder R, Lipes M. MR Imaging of insulitis in autoimmune diabetes. Magn Reson Med, 2002, 47:751-758.

4. Moore A, Grimm J, Josephson L, Weissleder R, Santamaria P. Noninvasive Imaging of insulitis lesions in the mouse model of type 1 Diabetes. Mol Imaging, 2002; 1: 236.

5. Grimm J, Potthast A, Wunder A, Moore A. Magnetic resonance imaging of the pancreas and pancreatic tumors in a mouse orthotopic model of human cancer, Int J Cancer, 2003, 106:806-811.

6. Moore A, Medarova Z, Potthast A, Dai G. In vivo targeting of underglycosylated MUC-1 tumor antigen using a multi-modal imaging probe, Cancer Res, 2004, 64:1821-1827.

7. Moore A, Grimm J, Han B, Santamaria P. Tracking the recruitment of diabetogenic CD8+ T cells to the pancreas in real time. Diabetes, 2004, in press.






			Anna Moore, Ph.D. 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 approaches to the measurement of beta-cell mass (BCM), early detection of lymphocyte infiltration in pancreatic islets during autoimmune attack and methods visualizing beta-cell apoptosis occurring in Type I and Type II diabetes mellitus. 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 and its consequences in animal models. Interest in this field is evident by ongoing studies by other investigators currently focused on imaging of transplanted islets in vivo using bioluminescence imaging. The results of these and other 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: 1. Moore A, Bonner-Weir S, Weissleder R. Non-invasive in vivo measurement of beta-cell mass in mouse model of diabetes. Diabetes, 2001, 50:2231-2236. 2. Moore A, Zhe P, Cory D, Högemann D, Lipes M, Weissleder R. High resolution imaging of infiltration of immune cells in mouse model of diabetes Type I. Proceedings of the meeting High Resolution Imaging in Small Animals 2001. Rockville, MD, 2001, Session 5, p.110. 3. Moore A, Sun PZ, Cory D, Högemann D, Weissleder R, Lipes M. MR Imaging of insulitis in autoimmune diabetes. Magn Reson Med, 2002, 47:751-758. 4. Moore A, Grimm J, Josephson L, Weissleder R, Santamaria P. Noninvasive Imaging of insulitis lesions in the mouse model of type 1 Diabetes. Mol Imaging, 2002; 1: 236. 5. Grimm J, Potthast A, Wunder A, Moore A. Magnetic resonance imaging of the pancreas and pancreatic tumors in a mouse orthotopic model of human cancer, Int J Cancer, 2003, 106:806-811. 6. Moore A, Medarova Z, Potthast A, Dai G. In vivo targeting of underglycosylated MUC-1 tumor antigen using a multi-modal imaging probe, Cancer Res, 2004, 64:1821-1827. 7. Moore A, Grimm J, Han B, Santamaria P. Tracking the recruitment of diabetogenic CD8+ T cells to the pancreas in real time. Diabetes, 2004, in press.