It has been longed hoped that transplanted islets could be imaged in living animals. This could allow the repeated assessment islet graft mass and provide an earlier diagnosis of islet rejection than measurements of blood glucose and C-peptide. The noninvasive imaging of transplanted islets in man now appears to be feasible, and awaits translation from rodents to nonhuman primates, and then to humans. We will test the hypotheses that; 1) the viral delivery of reporter genes, followed by optical and microPET imaging, provide new modalities to noninvasively monitor islet cell mass after intraportal islet transplantation and 2) optical and microPET imaging can detect islet rejection earlier than measurements of blood glucose and C-peptide levels. Furthermore, we will evaluate whether viral infection and long-term PET reporter expression is deleterious to the islet graft. Finally, as a step toward extending islet graft imaging to nonhuman primates, we will identify rAAV vectors that efficiently transduce nonhuman primate islets, and examine the effect of long-term imaging reporter gene expression on nonhuman primate islet function. Together, the results of this proposal will provide a significant advance towards translating islet imaging from a promising bench observation to one of clinical reality.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK068506-01
Application #
6816013
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Laughlin, Maren R
Project Start
2004-09-01
Project End
2006-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$230,500
Indirect Cost
Name
University of California Los Angeles
Department
Pharmacology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Lu, Yuxin; Dang, Hoa; Middleton, Blake et al. (2006) Long-term monitoring of transplanted islets using positron emission tomography. Mol Ther 14:851-6
Lu, Yuxin; Dang, Hoa; Middleton, Blake et al. (2006) Noninvasive imaging of islet grafts using positron-emission tomography. Proc Natl Acad Sci U S A 103:11294-9
Lu, Yuxin; Dang, Hoa; Middleton, Blake et al. (2004) Bioluminescent monitoring of islet graft survival after transplantation. Mol Ther 9:428-35