Long-term monitoring of transplanted islets using positron emission tomography.
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.
Lu
Yuxin
Y
Department of Molecular and Medical Pharmacology, University of California at Los Angeles School of Medicine, Los Angeles, CA 90095-1735, USA.
Dang
Hoa
H
Middleton
Blake
B
Campbell-Thompson
Martha
M
Atkinson
Mark A
MA
Gambhir
Sanjiv Sam
SS
Tian
Jide
J
Kaufman
Daniel L
DL
D000818:Animals; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D005822:Genetic Vectors / Q000235:genetics; D006085:Graft Survival / Q000235:genetics / Q000502:physiology; D018259:Herpesvirus 1, Human / Q000201:enzymology; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000000981:diagnostic imaging* / Q000379:methods; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009154:Mutation / Q000235:genetics; D049268:Positron-Emission Tomography / Q000379:methods*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014183:Transplantation, Heterologous
D013937:Thymidine Kinase