A porcine type 1 Diabetes Mellitus model, for non-invasive in vivo imaging of the glucagon-like peptide-1 receptor in the pancreas, using [68Ga]Ga-DO3A-VS-Cys40-conjugated synthetic exendin-4 in PET-CT

摘要: Diabetes mellitus is a rising epidemic throughout the world and there currently great interest in quantifying beta-cell mass (BCM) vivo non-invasively. In present experiment, feasibility of imaging glucagon-like peptide-1 receptor (GLP-1R) beta-cells was examined, using positron emission tomography (PET) tracer [68Ga]Ga-DO3A-VS-Cys40-exendin-4 as marker, native pancreatic porcine diabetic animal model healthy controls. Eight Swedish high-health domestic pigs were randomly assigned to be either controls or made streptozotocin (STZ). The experiment proceeded during eight weeks, starting with an acclimatisation period. Once had been socialised they underwent surgery for insertion jugular vein catheter, allowing induction diabetes STZ, intravenous (i.v.) injections stress-free blood sampling. Development confirmed by clinical examinations, glucose values insulin-staining sections post mortem. The insulin treated responded well. PET-CT (PET-computed tomography) examinations performed on insulin-treated pigs. At beginning scan, oxygen-15 labelled water ([15O]WAT) injected i.v. measure tissue perfusion pancreas kidneys. specific binding GLP-1R assessed administration compound giving baseline image. This followed competing high dose synthetic exendin-4 new sequence. humanely euthanised 0–6 days after examination full mortem all pigs. Diabetes successfully induced, immunohistochemical (IHC) staining insulin. An important incidental finding, examination, that immediately induced significant tachycardia both at low dose. PET scans showed reduced kidneys GLP-1R-mediated uptake detected surprisingly, did not differ between two groups. Thus, significantly selective destruction suitable target Additionally, this shows how pig can diabetic, properly anaesthetised several hours, which makes further research.