1. ¹Department of Molecular and Medical Pharmacology, University of California at Los Angeles School of Medicine, Los Angeles, CA 90095-1735, USA
2. ²Department of Pathology, University of Florida, Gainesville, FL 32611, USA
3. ³Departments of Radiology and Bioengineering Bio-X Program, Molecular Imaging Program at Stanford, Stanford University, Stanford, CA 94305, USA

Correspondence: Daniel L. Kaufman, Fax: +1 310 825 6267. E-mail: dkaufman@mednet.ucla.edu

Received 9 May 2006; Revised 3 August 2006; Accepted 17 August 2006.

Abstract

Islet transplantation can restore glucose homeostasis in those with type 1 diabetes; however, most recipients eventually lose graft function. A noninvasive method to monitor islets following transplantation would enable assessment of their survival and aid the development of therapeutics to prolong graft survival. Here, we show that recombinant lentivirus can be used to engineer human islets to express a positron emission tomography (PET) reporter gene. Following transplantation into mice, transduced islets could be imaged in vivo using microPET and a radiolabeled probe approved by the FDA for clinical use in humans. The magnitude of signal from engineered islets implanted into the axillary cavity reflected the implanted islet mass. Signals from implanted islets decreased by approximately one-half during the first few weeks following transplantation, which may reflect islet cell death shortly after transplantation. Thereafter, the magnitude of signals from the implanted islets remained fairly constant when the recipients were repetitively reimaged over 90 days. Histological analysis of the implants showed healthy islets with PET reporter-expressing cells distributed throughout the islet architecture. These studies suggest that PET imaging of lentivirus-transduced islets could provide a safe and feasible method for long-term monitoring of islet graft survival.