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Diabetologia
Published in: Diabetologia 10/2018

01-10-2018 | Article

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

Authors: Andrew T. Templin, Daniel T. Meier, Joshua R. Willard, Tami Wolden-Hanson, Kelly Conway, Yin-Guo Lin, Patrick J. Gillespie, Krister B. Bokvist, Giorgio Attardo, Steven E. Kahn, Donalyn Scheuner, Rebecca L. Hull

Published in: Diabetologia | Issue 10/2018

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Abstract

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 hIAPP 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 hIAPP 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 < 0.05). In hIAPP transgenic and non-transgenic mice fed a high-fat diet for 1 year, intravenous administration of florbetapir followed by PET scanning showed that the florbetapir signal was significantly higher in amyloid-laden hIAPP transgenic vs amyloid-free non-transgenic pancreases in vivo during the first 5 min of the scan (36.83 ± 2.22 vs 29.34 ± 2.03 standardised uptake value × min, p < 0.05). Following PET, pancreases were excised and florbetapir uptake was determined ex vivo by γ counting. Pancreatic uptake of florbetapir was significantly correlated with the degree of islet amyloid deposition, the latter assessed by histochemistry (r = 0.74, p < 0.001).

Conclusions/interpretation

Florbetapir binds to islet amyloid deposits in a specific and quantitative manner. In the future, florbetapir may be useful as a non-invasive tool to identify islet amyloid deposits in humans.
Appendix
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Metadata
Title
Use of the PET ligand florbetapir for in vivo imaging of pancreatic islet amyloid deposits in hIAPP transgenic mice
Authors
Andrew T. Templin
Daniel T. Meier
Joshua R. Willard
Tami Wolden-Hanson
Kelly Conway
Yin-Guo Lin
Patrick J. Gillespie
Krister B. Bokvist
Giorgio Attardo
Steven E. Kahn
Donalyn Scheuner
Rebecca L. Hull
Publication date
01-10-2018
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 10/2018
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-018-4695-y

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