Diabetes

We are using techniques in Molecular Imaging, which utilizes contrast agents based on molecular and cellular biology techniques in combination with diagnostic imaging modalities, to examine pancreatic islet function in vivo. Our interests range from detecting changes in islet function that precede the onset of diabetes, to examining the molecular processes of engraftment and vascularization of islet transplants, to evaluating the role of stem cells in generating new islets. To this end, we are utilizing novel imaging reporter genes for PET and MRI, as well as targeted probes for PET and SPECT imaging.

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Imaging gene expression in transplanted pancreatic beta cells using SPECT/CT
Researchers
S. Dhanvantari
molecular imaging, diabetes
T.-Y. Lee
PET/CT
M.S. Kovacs
PET radiochemistry

Technologies
3T PET/MR
Cyclotron & PET Radiochemistry
Molecular Imaging
PET/CT
SPECT/CT

Collaborators
D. Hill
diabetes
P. Foster
MRI, cellular imaging
D. White
transplantation
J. Koropatnick
molecular biology
R.G. Wells
PET/SPECT physics
Future Directions

Our efforts in synthesizing targeted probes have led to an application for funding from an industrial partner. We hope that our targeted probe, one that recognizes a cell surface receptor on the beta cell, will lead to clinical trials in imaging the pancreatic islet in vivo in humans at risk for developing diabetes. With Dr. Hill's experience with diabetic patient clinical trials, we anticipate having ready access to testing our probes in humans. Our transgenic mouse model will be a unique and valuable tool with which to screen therapies for islet regeneration and development. We are seeking funding to develop molecular imaging technologies to non-invasively detect the engraftment and vascularization of transplanted pancreatic islets, and their development from stem cell progenitors.

Key Accomplishments

The diabetes group focuses on molecular imaging of the pancreatic islet. We have used reporter genes to image pancreatic islet transplants using dual-isotope SPECT (J. Nucl. Med. 49:94-102, 2008) and we were the first to develop a transgenic mouse in which changes in beta cell mass can be detected by PET molecular imaging (Mol. Imaging Biol., 2010, in press). Our group is designing and testing targeted probes for the imaging of islets using PET and SPECT (Bioorg. Med. Chem., 18:1265-72, 2010). We have also used MRI to detect transplanted pancreatic islets in vivo (Diabetes, 55:2931-8, 2006).

Our group works closely with Dr. David Hill, whose lab has made significant inroads in investigating mechanisms of islet development. Dr. Hill is also actively involved with collaborative groups in several clinical trials assessing lifestyle intervention in the prevention of gestational diabetes, prevention of cardiovascular complications in diabetes, and examining strategies to prevent progression of Type 2 diabetes in pediatric populations.

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