Non-invasive quantification of the beta cell mass by SPECT with 111In-labelled exendin

Abstract

Aims/hypothesis A reliable method for in vivo quantification of pancreatic beta cell mass (BCM) could lead to further insight into the pathophysiology of diabetes. The glucagonlike peptide 1 receptor, abundantly expressed on beta cells, may be a suitable target for imaging. We investigated the potential of radiotracer imaging with the GLP-1 analogue exendin labelled with indium-111 for determination of BCM in vivo in a rodent model of beta cell loss and in patients with type 1 diabetes and healthy individuals. MethodsThe targeting of 111 In-labelled exendin was examined in a rat model of alloxan-induced beta cell loss. Rats were injected with 15 MBq 111 In-labelled exendin and single photon emission computed tomography (SPECT) acquisition was performed 1 h post injection, followed by dissection, biodistribution and ex vivo autoradiography studies of pancreatic sections. BCM was determined by morphometric analysis after staining with an anti-insulin antibody. For clinical evaluation SPECT was acquired 4, 24 and 48 h after injection of 150 MBq 111 In-labelled exendin in five patients with type 1 Maarten Brom and Wietske Woliner-van der Weg contributed equally to this study. Diabetologia (2014) 57:950-959 DOI 10.1007 diabetes and five healthy individuals. The tracer uptake was determined by quantitative analysis of the SPECT images. Results In rats, 111 In-labelled exendin specifically targets the beta cells and pancreatic uptake is highly correlated with BCM. In humans, the pancreas was visible in SPECT images and the pancreatic uptake showed high interindividual variation with a substantially lower uptake in patients with type 1 diabetes. Conclusions/interpretation These studies indicate that 111 Inlabelled exendin may be suitable for non-invasive quantification of BCM.

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

“…111 Inexendin-3 showed low accumulation in blood, heart, spleen, and liver (maximum, 0.1 percentage injected dose [%ID]/g). Uptake was observed in stomach, duodenum, and lungs (0.74 6 0.45, 0.51 6 0.32, and 10.0 6 5.28 %ID/g, respectively), which corresponds with previous observations (15). Kidney accumulation was high (31.9 6 11.5 %ID/g) and was not GLP-1R-mediated.…”

“…It has previously been demonstrated that targeting of GLP-1R with radiolabeled exendin is an elegant method for imaging b-cells, mainly in insulinoma models (14,19) and the native pancreas (15). This strategy was applied by Wu et al, who used PET after injection of exendin-4 labeled with 64 Cu or 18 F to visualize islets transplanted into the liver (9,20).…”

“…Finally, Bright-DAB (BS04500; Immunologic BV) was used to visualize peroxidase activity. Microautoradiography to visualize tracer accumulation was performed on 4-mm sections as described by Brom et al (15).…”

Deletion of β-Arrestin2 in Mice Limited Pancreatic β-Cell Expansion under Metabolic Stress through Activation of the JNK Pathway

“…In-labeled exendin] have been utilized in the field of human β-cell image studies (25)(26)(27). Likewise, BLI has been widely used with luciferase transgenic mice to evaluate β-cell mass under both normal and pathological conditions (17,28).…”

“…However, quantification of β-cell mass in vivo is relatively difficult due to the lack of reliable and noninvasive biomarkers for cells (24). Recently, the use of in vivo imaging techniques including positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) with isotope-labeled ligands [such as In-labeled exendin] have been utilized in the field of human β-cell image studies (25)(26)(27). Likewise, BLI has been widely used with luciferase transgenic mice to evaluate β-cell mass under both normal and pathological conditions (17,28).…”