Purpose

The glucagon-like peptide-1 receptor (GLP-1R) has been proposed as a target for molecular imaging of beta cells. The feasibility of non-invasive imaging and quantification of GLP-1R in pancreas using the positron emission tomography (PET) tracer [⁶⁸Ga]Ga-DO3A-VS-Cys⁴⁰-Exendin-4 in non-diabetic and streptozotocin (STZ)–induced diabetic pigs treated with insulin was investigated.

Methods

Non-diabetic (n = 4) and STZ-induced diabetic pigs (n = 3) from the same litter were examined. Development of diabetes was confirmed by blood glucose values, clinical examinations and insulin staining of pancreatic sections post mortem. Tissue perfusion in the pancreas and kidneys was evaluated by [¹⁵O]water PET/computed tomography (CT) scans. The in vivo receptor specificity of [⁶⁸Ga]Ga-DO3A-VS-Cys⁴⁰-Exendin-4 was assessed by administration of either tracer alone or by competition with 3–6.5 μg/kg of Exendin-4. Volume of distribution and occupancy in the pancreas were quantified with a single tissue compartment model.

Results

[¹⁵O]water PET/CT examinations showed reduced perfusion in the pancreas and kidneys in diabetic pigs. [⁶⁸Ga]Ga-DO3A-VS-Cys⁴⁰-Exendin-4 uptake in the pancreas of both non-diabetic and diabetic pigs was almost completely abolished by co-injection of unlabeled Exendin-4 peptide. [⁶⁸Ga]Ga-DO3A-VS-Cys⁴⁰-Exendin-4 uptake did not differ between non-diabetic and diabetic pigs. In all animals, administration of the tracer resulted in an immediate increase in the heart rate (HR).

Conclusion

Pancreatic uptake of [⁶⁸Ga]Ga-DO3A-VS-Cys⁴⁰-Exendin-4 was not reduced by destruction of beta cells in STZ-induced diabetic pigs.