PET-CT Scan Method to Monitor Pancreatic B-Cell Loss in Diabetes Mellitus
Status:
Completed
Trial end date:
2008-07-01
Target enrollment:
Participant gender:
Summary
The pancreas is an organ that plays major roles in the digestion of food. A part of the
pancreas called islet beta-cells produces insulin, which regulates the amount of glucose (a
sugar) present in the blood at all times. Type-1 Diabetes Mellitus (T1DM), an autoimmune
disorder characterized by destruction of pancreatic islet beta-cells (the cells that produce
insulin), affects at least a million individuals in the US alone. In T1DM, a type of white
blood cells called T lymphocytes attacks and destroys the pancreatic islet beta-cells,
leading to a loss of insulin, an increase in blood glucose, and a dependence on insulin
injections for survival. Despite rigorous control of blood sugar, the majority of diabetic
patients develop serious complications including retinopathy, nephropathy, neuropathy,
microangiopathy and strokes.
Non-invasive methods to monitor pancreatic beta-cell loss associated with type-1 diabetes
mellitus (T1DM) could improve early diagnosis, provide tools to measure responsiveness to new
therapies, and evaluate the efficiency of pancreatic transplantation and graft survival.
Our goal is to develop a non-invasive PET-CT imaging method based on binding of a molecule
(18F-fallypride) for tracking beta-cell loss during the progression of T1DM. In preliminary
studies we demonstrated specific binding of 18F-fallypride to D2 receptors in rat pancreatic
sections and we demonstrated that the loss of pancreatic beta cells in streptozotocin-treated
rats was associated with a corresponding decrease in 18F-fallypride binding to pancreatic
sections. A preliminary 18F-fallypride PET-CT study done by a collaborator in Ohio on a
healthy volunteer, revealed 18F-fallypride-uptake by the pancreas that was distinguishable
from surrounding tissues. Aim-1 of our project will measure the variability of 18F-fallypride
PET-scanning of the pancreas in six healthy volunteers scanned twice with an interval of 4-6
weeks. In Aim-2 of our project, we will compare fallypride PET-CT scans of 12 patients with
long-standing T1DM (nearly all beta cells destroyed) with 12 age- and sex-matched healthy
volunteers. If we are able to distinguish between the two groups, we will in future (a)
optimize the method so as to be able to detect a 20-30% loss of beta cells, and (b) perform
PET-CT studies in new-onset T1DM patients and in at-risk first degree relatives of T1DM
patients.