Assessment of Beta Cell Mass in Type 1 Diabetes With 11C-Dihydrotetrabenazine and PET Scan

Diabetes is a metabolic disorder in which pancreatic insulin producing B-cells (located in cell clusters called the islets of Langerhans) no longer produce sufficient insulin to maintain an individual's blood sugar concentration within the normal range. Insufficient B-cell function can be caused by an autoimmune killing of the B-cells in type 1 diabetes mellitus (T1DM), or by poorly understood mechanisms in type 2 diabetes mellitus (T2DM). Regardless of the underlying cause, the development of new diabetes treatments is limited by our current inability to objectively measure B-cell mass. We propose testing a previously used clinical radioligand, dihydrotetrabenazine (DTBZ), as a Positron Emission Tomography (PET) imaging agent for its ability to non-invasively measure B-cell mass in humans. We will study 30 patients, 10 with T1DM, 10 with normal glucose homeostasis, and 5 with a history of T1DM, but successfully restored glucose homeostasis following whole pancreas transplantation. Prior to the PET scans, each patient will undergo metabolic testing to characterize their glucose homeostasis and insulin producing capacity. The pancreas will be initially identified in each patient with high-resolution magnetic resonance imaging (MRI). Then, using anatomical landmarks identified by the MRI, the subject will undergo DTBZ-PET imaging. We predict that the radioactivity signal in the pancreas from the DTBZ-PET images will be significantly different between control subjects and T1DM subjects. Further, we predict that the DTBZ-PET images obtained in individuals with functioning pancreas allografts (and such patients have two pancreases- their native pancreas and their pancreas allografts) will reveal signal intensities from the two glands that correlates closely with each gland's insulin producing capacity. Should these studies suggest DTBZ has merit as a beta cell imaging agent, we will expand the study to include patients with T2DM.