Use of the PET ligand florbetapir for in vivo imaging of pancreatic islet amyloid deposits in hIAPP transgenic mice

• Published in: Diabetologia 2018-10, Vol.61 (10), p.2215-2224
• Main Authors: Templin, Andrew T., Meier, Daniel T., Willard, Joshua R., Wolden-Hanson, Tami, Conway, Kelly, Lin, Yin-Guo, Gillespie, Patrick J., Bokvist, Krister B., Attardo, Giorgio, Kahn, Steven E., Scheuner, Donalyn, Hull, Rebecca L.
• Format: Article
• Language: English
• Subjects: Amylin; Amyloid - chemistry; Aniline Compounds - pharmacology; Animals; Autoradiography; Beta cells; Body Composition; Calorimetry, Indirect; Cell death; Deposits; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Ethylene Glycols - pharmacology; Fibrils; Fluorine Radioisotopes - pharmacology; Gene Expression Regulation; Glucose Clamp Technique; Glucose Tolerance Test; High fat diet; Human Physiology; Hypothalamus - metabolism; Insulin - metabolism; Insulin Resistance; Internal Medicine; Intravenous administration; Islets of Langerhans - diagnostic imaging; Ligands; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuroimaging; Pancreas; Pharmaceuticals; Polymerase Chain Reaction; Positron emission tomography; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism; Radioisotopes; Rodents; Signal Transduction; Transgenic animals; Transgenic mice
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-018-4695-y

Aims/hypothesis Islet amyloid deposits contribute to beta cell dysfunction and death in most individuals with type 2 diabetes but non-invasive methods to determine the presence of these pathological protein aggregates are currently not available. Therefore, we examined whether florbetapir, a radiopharmaceutical agent used for detection of amyloid-β deposits in the brain, also allows identification of islet amyloid in the pancreas. Methods Saturation binding assays were used to determine the affinity of florbetapir for human islet amyloid polypeptide (hIAPP) aggregates in vitro. Islet amyloid-prone transgenic mice that express h IAPP in their beta cells and amyloid-free non-transgenic control mice were used to examine the ability of florbetapir to detect islet amyloid deposits in vitro, in vivo and ex vivo. Mice or mouse pancreases were subjected to autoradiographic, histochemical and/or positron emission tomography (PET) analyses to assess the utility of florbetapir in identifying islet amyloid. Results In vitro, florbetapir bound synthetic hIAPP fibrils with a dissociation constant of 7.9 nmol/l. Additionally, florbetapir bound preferentially to amyloid-containing h IAPP transgenic vs amyloid-free non-transgenic mouse pancreas sections in vitro, as determined by autoradiography (16,475 ± 5581 vs 5762 ± 575 density/unit area, p