Noninvasive Imaging of Islet Transplants with 111In-Exendin-3 SPECT/CT

• DOI: 10.2967/jnumed.115.166330
• Publication Date: 2016-01-22T02:55:04Z
• Authors: Inge van der Kroon; Karolina Andralojc; Stefanie M.A. Wil...; Desirée Bos; Lieke Joosten; Otto C. Boerman; Maarten Brom; Martin Gotthardt
• Keywords: Single Photon Emission Computed Tomography Computed Tomography; Radboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life Sciences; Indium Radioisotopes; Islets of Langerhans Transplantation; Glucagon-Like Peptide-1 Receptor; Rats; 3. Good health; 03 medical and health sciences; Radboudumc 14: Tumours of the digestive tract RIMLS: Radboud Institute for Molecular Life Sciences; 0302 clinical medicine; Animals; Female; Tissue Distribution; Radboudumc 0: Other Research RIHS: Radboud Institute for Health Sciences; Peptides

Islet transplantation is a promising treatment for type 1 diabetic patients. However, there is acute as well as chronic loss of islets after transplantation. A noninvasive imaging method that could monitor islet mass might help to improve transplantation outcomes. In this study, islets were visualized after transplantation in a rat model with a dedicated small-animal SPECT scanner by targeting the glucagonlike peptide-1 receptor (GLP-1R), specifically expressed on β-cells, with (111)In-labeled exendin-3.Targeting of (111)In-exendin-3 to GLP-1R was tested in vitro on isolated islets of WAG/Rij rats. For in vivo evaluation, 400 or 800 islets were transplanted into the calf muscle of WAG/Rij rats (6-8 wk old). Four weeks after transplantation, SPECT/CT images were acquired 1 h after injection of (111)In-labeled exendin-3. After SPECT acquisition, the muscles containing the transplant were analyzed immunohistochemically and autoradiographically.The binding assay, performed on isolated islets, showed a linear correlation between the number of islets and (111)In-exendin-3 accumulation (Pearson r = 0.98). In vivo, a 1.70 ± 0.44-fold difference in tracer uptake between 400 and 800 transplanted islets was observed. Ex vivo analysis of the islet transplant showed colocalization of tracer accumulation on autoradiography, with insulin-positive cells and GLP-1R expression on immunohistochemistry.(111)In-exendin-3 accumulates specifically in the β-cells after islet transplantation and is a promising tracer for noninvasive monitoring of the islet mass.