Abstract
Pancreatic islet transplantation is a promising therapy for patients with type 1 diabetes. However, the duration of long-term graft survival is limited due to inflammatory as well as non-inflammatory processes and routine clinical tests are not suitable to monitor islet survival. 111In-exendin-SPECT (single photon emission computed tomography) is a promising method to non-invasively image islets after transplantation and has the potential to help improve the clinical outcome. Whether 111In-exendin-SPECT allows detecting small differences in beta-cell mass (BCM) and measuring the actual volume of islets that were successfully engrafted has yet to be demonstrated. Here, we evaluated the performance of 111In-exendin-SPECT using an intramuscular islet transplantation model in C3H mice. In vivo imaging of animals transplanted with 50, 100, 200, 400 and 800 islets revealed an excellent linear correlation between SPECT quantification of 111In-exendin uptake and insulin-positive area of islet transplants, demonstrating that 111In-exendin-SPECT specifically and accurately measures BCM. The high sensitivity of the method allowed measuring small differences in graft volumes, including grafts that contained less than 50 islets. The presented method is reliable, convenient and holds great potential for non-invasive monitoring of BCM after islet transplantation in humans.
Highlights
Quantitative analysis of SPECT signal originating from the transplant revealed differences in 111In-exendin-3 accumulation depending on the number of initially transplanted islets, where the uptake was 5.9 kBq ± 2.4, 22.9 kBq ± 4.8, 30.1 kBq ± 10.1, 60.9 kBq ± 9.8 and 88.7 kBq ± 11.5, in muscles transplanted with 50, 100, 200, 400 and 800 islets, respectively (Fig. 2B)
The aim of this study was to evaluate the relation between 111In-exendin uptake in islet transplants compared to actual beta-cell mass (BCM) in a muscle model of islet transplantation
This high sensitivity in combination with the excellent correlation of BCM and tracer uptake demonstrate the potential of this method to quantify small differences in viable beta-cell volume
Summary
Whether 111Inexendin-SPECT allows detecting small differences in beta-cell mass (BCM) and measuring the actual volume of islets that were successfully engrafted has yet to be demonstrated. In order to monitor the graft volume and optimize new strategies for beta-cells replacement a non-invasive technology to visualize viable transplanted islets in vivo is warranted. Such a method should be quantitative and sensitive in order to allow the detection of small changes in the number of surviving islets. First results of PET imaging of an islet graft were published in 2006, using islets which were transfected with an insulin promoter-dependent reporter gene that leads to trapping of the PET probe 18F-FHBG www.nature.com/scientificreports/
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