Toward development of imaging modalities for islets after transplantation: Insights from the national institutes of health workshop on beta cell imaging

Pancreatic islet transplantation can provide insulin independence and near normal glucose control in selected patients with type 1 diabetes mellitus. However, in most cases, achieving insulin independence necessitates the use of at least two donor pancreases per recipient and the rate of insulin independence may decline after transplantation. To better understand the fate of transplanted islets and the relationship between transplanted islet mass, graft function, and overall glucose homeostasis, an accurate and reproducible method of imaging islets in vivo is needed. Recent advances in noninvasive imaging techniques such as magnetic resonance imaging, positron emission tomography, and other imaging modalities show great promise as potential tools to monitor islet number, mass, and function in the clinical setting. A recent international workshop, "Imaging the Pancreatic Beta Cell," sponsored by the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Juvenile Diabetes Research Foundation International focused on these emerging efforts to develop novel ways of imaging pancreatic beta cells in vivo. Potential clinically applicable techniques include the use of directed magnetic resonance contrast agents such as lanthanides (Ln(3+)) and manganese (Mn(2+)) or magnetic resonance imaging probes such as superparamagnetic iron oxide nanoparticles. Potential techniques for positron emission tomography imaging include the use of beta cell-specific antibodies, or pharmacologic agents such as glyburide analogs, or d-mannoheptulose. Optical imaging techniques are also being used to evaluate various aspects of beta cell metabolism including intracellular Ca(2+) flux, glucokinase activity, and insulin granular exocytosis. The consensus among investigators at the imaging workshop was that an accurate and reproducible in vivo measure of functional islet mass is critically needed to further the strides that have been made in both islet transplantation and diabetes research as a whole. Such measures would potentially allow the assessment of islet engraftment and the early recognition of graft loss, leading to greater improvements in islet graft survival and function.