exenatide and 1-4-7-10-tetraazacyclododecane--1-4-7-10-tetraacetic-acid

(111)In-DOTA-exendin-4 SPECT/CT has been shown to be highly efficient in the detection of insulinomas. We aimed at determining whether novel PET/CT imaging with [Nle(14),Lys(40)(Ahx-DOTA-(68)Ga)NH2]exendin-4 ((68)Ga-DOTA-exendin-4) is feasible and sensitive in detecting benign insulinomas.. (68)Ga-DOTA-exendin-4 PET/CT and (111)In-DOTA-exendin-4 SPECT/CT were performed in a randomized cross-over order on 5 patients with endogenous hyperinsulinemic hypoglycemia. The gold standard for comparison was the histologic diagnosis after surgery.. In 4 patients histologic diagnosis confirmed a benign insulinoma, whereas one patient refused surgery despite a positive (68)Ga-DOTA-exendin-4 PET/CT scan. In 4 of 5 patients, previously performed conventional imaging (CT or MR imaging) was not able to localize the insulinoma. (68)Ga-DOTA-exendin-4 PET/CT correctly identified the insulinoma in 4 of 4 patients, whereas (111)In-DOTA-exendin-4 SPECT/CT correctly identified the insulinoma in only 2 of 4 patients.. These preliminary data suggest that the use of (68)Ga-DOTA-exendin-4 PET/CT in detecting hidden insulinomas is feasible.

Topics: Adult; Cross-Over Studies; Diagnostic Imaging; Exenatide; Female; Gallium Radioisotopes; Glucose; Heterocyclic Compounds, 1-Ring; Humans; Immunohistochemistry; Insulinoma; Male; Middle Aged; Multimodal Imaging; Peptides; Pilot Projects; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Venoms; Whole Body Imaging

Topics: Exenatide; Female; Gallium Radioisotopes; Heterocyclic Compounds, 1-Ring; Humans; Hyperinsulinism; Hypoglycemia; Insulinoma; Middle Aged; Pancreas; Pancreatic Neoplasms; Pancreaticojejunostomy; Peptides; Positron Emission Tomography Computed Tomography; Treatment Outcome; Venoms

The purpose of this study was to evaluate the binding specificity of the radiolabeled glucagon-like peptide 1 receptor (GLP-1R) agonist (Lys⁴⁰(DOTA)NH₂)Exendin-4 in the pancreas using a combination of ex vivo autoradiography and immunohistochemistry.. Sprague-Dawley rats were administered [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 i.v. with or without unlabeled Exendin (9-39) to determine binding specificity. Similar experiments were performed using Zucker diabetic fatty (ZDF) and Zucker lean (ZLC) rats. Animals were euthanized and the pancreas was extracted, immediately frozen, and sectioned. The sections were apposed to phosphor imaging plates, scanned, and immunostained for insulin.. Co-registration of the autoradiographic and immunohistochemical images revealed that [⁶⁴Cu] (Lys⁴⁰(DOTA)NH₂)Exendin-4 specific binding was restricted to islet cells. This binding was blocked by the co-administration of Exendin(9-39) indicating that the radiotracer uptake is mediated by GLP-1R. Uptake of [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 was greatly decreased in the pancreas of ZDF rats.. Ex vivo autoradiography results using [⁶⁴Cu](Lys⁴⁰(DOTA)NH₂)Exendin-4 suggest that GLP-1R agonists based on Exendin-4 are attractive PET ligands for the in vivo determination of β-cell mass.

Topics: Animals; Autoradiography; Copper Radioisotopes; Exenatide; Glucagon-Like Peptide-1 Receptor; Heterocyclic Compounds, 1-Ring; Immunohistochemistry; Insulin-Secreting Cells; Male; Molecular Imaging; Peptides; Radionuclide Imaging; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Rats, Zucker; Receptors, Glucagon; Venoms