In vivo visualization of transplanted islets in rats by SPECT with In-111-Exendin-3

Objectives There is an urgent need for a method that would noninvasively determine beta cell mass (BCM) loss after transplantation in vivo in patients. We have developed a noninvasive imaging technique that specifically visualizes BCM in vivo. This method is based on the targeting of the glucagon-like peptide 1 receptor (GLP-1R) which is expressed at high levels on pancreatic beta cells. Our tracer specifically binds to the GLP-1R: In-111-Exendin-3. We examined whether intramuscularly transplanted islets in rats could be visualized by SPECT after i.v. injection with radiolabeled Exendin-3.

Methods Islets (250,500,750,1000) were isolated from Wag/Rij rats and transplanted in the thigh muscle and vehicle was injected into the contralateral muscle as a control. Two,7,14,21,28,42 and 77 days after transplantation In-111-Exendin-3 was injected i.v. and SPECT images were acquired 1h post injection using a U-SPECT II microSPECT scanner. At the last day the rats were euthanized and biodistribution, microautoradiography (MAR) and immunohistochemistry (IHC) was performed.

Results The transplanted islets were clearly visualized with SPECT at all time points (Fig.1). Tracer uptake was linearly correlated with number of islets transplanted (Fig.3). After graft was established, uptake in the islets was stable over time (Fig.2). Ex vivo MAR showed high uptake of In-111-Exendin-3 in the islets. IHC confirmed that islets were viable and produced insulin. Tracer uptake in the muscle with islets was higher than uptake in the control muscle (0.27±0.06%ID vs 0.07±0.02%ID).

Conclusions Transplanted islets were clearly delineated with SPECT after injection of In-111-Exendin-3. SPECT images can be analyzed quantitatively, enabling longitudinal monitoring of BCM over time with a linear correlation of SPECT quantification with the number of islets transplanted. In-111-Exendin-3 could potentially be used for noninvasive BCM determination.

Research Support Supported by NIH grant 1R01AG030328-01 and the European Community's 7th FP (FP7/2007-2013) under grant agreement n° 222980