BCM estimates with [18F]Fluorylpropyl-DTBZ

Type 1 diabetes results from autoimmune destruction of pancreatic beta cell mass. Early in disease, beta cell loss proceeds almost silently until there is insufficient beta cell mass to meet the metabolic needs of insulin production, when hyperglycemia and other symptoms appear. The lack of reliable measurements of beta cell mass and of the bodies true capacity to produce insulin, constitute a serious dilemma facing health care professionals and the pharmaceutical industry. Recent advances in imaging science, molecular imaging chemistry as well as a broader understanding of basic islet biology now allow the collection of quantitative information about beta-cells deep within the pancreas. In previous studies, we identified a biomarker of beta cell mass, called vesicular monoamine transporter type 2 (VMAT2), which can be measured by positron emission tomography (PET). PET is a tomographic imaging technique that allows us to make non-invasive measurements of the beta cell biomarker using a radiopharmaceutical that binds to VMAT2. In animal studies, a loss of binding of the radiopharmaceutical in pancreas preceded the development of symptoms of diabetes and later paralleled the rise in blood sugar that hallmarks the onset of clinical disease. We have also tested our beta cell monitoring technique in a small human clinical trial where we able to see differences in beta cell mass between health controls and patients that have had type 1 diabetes for more than twenty years. In this proposal we wish to test a novel radiopharmaceutical for measuring BCM. This novel radiopharmaceutical (F18) fluorylpropyl-DTBZ, represents a significant advantage over radiopharmaceuticals we have worked with in the past because it can be easily distributed to PET centers across the country and may be better tailored chemically for measuring the beta cell mass biomarker. The ability to non-invasively measure the mass of insulin producing beta cells will most likely be of value towards characterizing new drugs and refining the diagnosis and treatment of this disease.