Quantification of β-Cell Mass in Intramuscular Islet Grafts Using Radiolabeled Exendin-4.
BACKGROUND
There is an increasing interest in alternative implantation sites to the liver for islet transplantation. Intramuscular implantation has even been tested clinically. Possibilities to monitor β-cell mass would be of huge importance not only for the understanding of islet engraftment but also for the decision of changing the immunosuppressive regime. We have therefore evaluated the feasibility of quantifying intramuscular β-cell mass using the radiolabeled glucagon like peptide-1 receptor agonist DO3A-VS-Cys40-Exendin-4.


METHODS
One hundred to 400 islets were transplanted to the abdominal muscle of nondiabetic mice. After 3 to 4 weeks, 0.2 to 0.5 MBq [177Lu]DO3A-VS-Cys40-Exendin-4 was administered intravenously. Sixty minutes postinjection abdominal organs and graft bearing muscle were retrieved, and the radioactive uptake measured in a well counter within 10 minutes. The specific uptake in native and transplanted islets was assessed by autoradiography. The total insulin-positive area of the islet grafts was determined by immunohistochemistry.


RESULTS
Intramuscular islet grafts could easily be visualized by this tracer, and the background uptake was very low. There was a linear correlation between the radioactivity uptake and the number of transplanted islets, both for standardized uptake values and the total radiotracer uptake in each graft (percentage of injected dose). The quantified total insulin area of surviving β cells showed an even stronger correlation to both standardized uptake values (R= 0.96,P= 0.0002) and percentage of injected dose (R= 0.88,P= 0.0095). There was no correlation to estimated α cell mass.


CONCLUSIONS
[177Lu]DO3A-VS-Cys40-Exendin-4 could be used to quantify β-cell mass after experimental intramuscular islet transplantation. This technique may well be transferred to the clinical setting by exchanging Lutetium-177 radionuclide to a positron emitting Gallium-68.
Department of Medical Cell Biology, Uppsala University, Sweden.; Department of Medical Sciences, Uppsala University, Sweden.
Daniel
D
Espes
Division of Molecular Imaging, Department of Medicinal Chemistry, Uppsala University, Sweden.
Ramkumar
R
Selvaraju
Division of Molecular Imaging, Department of Medicinal Chemistry, Uppsala University, Sweden.; PET Center, Uppsala University Hospital, Sweden.
Irina
I
Velikyan
Division of Molecular Imaging, Department of Medicinal Chemistry, Uppsala University, Sweden.
Martin
M
Krajcovic
Department of Medical Cell Biology, Uppsala University, Sweden.; Department of Medical Sciences, Uppsala University, Sweden.
Per-Ola
PO
Carlsson
Division of Molecular Imaging, Department of Medicinal Chemistry, Uppsala University, Sweden.; Turku PET center, Faculty of Natural Sciences and Technology, Åbo Akademi, Turku, Finland.
Olof
O
Eriksson