Jump to main content
Jump to site search


Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas

Author affiliations

Abstract

Global rates of diabetes mellitus are increasing, and treatment of the disease consumes a growing proportion of healthcare spending across the world. Pancreatic β-cells, responsible for insulin production, decline in mass in type 1 and, to a more limited degree, in type 2 diabetes. However, the extent and rate of loss in both diseases differs between patients resulting in the need for the development of novel diagnostic tools, which could quantitatively assess changes in mass of β-cells over time and potentially lead to earlier diagnosis and improved treatments. Exendin-4, a potent analogue of glucagon-like-peptide 1 (GLP-1), binds to the receptor GLP-1R, whose expression is enriched in β-cells. GLP-1R has thus been used in the past as a means of targeting probes for a wide variety of imaging modalities to the endocrine pancreas. However, exendin-4 conjugates designed specifically for MRI contrast agents are an under-explored area. In the present work, the synthesis and characterization of an exendin-4-dota(ga)-Gd(III) complex, GdEx, is reported, along with its in vivo behaviour in healthy and in β-cell-depleted C57BL/6J mice. Compared to the ubiquitous probe, [Gd(dota)], GdEx shows selective uptake by the pancreas with a marked decrease in accumulation observed after the loss of β-cells elicited by deleting the microRNA processing enzyme, DICER. These results open up pathways towards the development of other targeted MRI contrast agents based on similar chemistry methodology.

Graphical abstract: Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas

Back to tab navigation

Supplementary files

Article information


Submitted
29 Jan 2020
Accepted
07 Mar 2020
First published
19 Mar 2020

Dalton Trans., 2020, Advance Article
Article type
Paper

Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas

T. J. Clough, N. Baxan, E. J. Coakley, C. Rivas, L. Zhao, I. Leclerc, A. Martinez-Sanchez, G. A. Rutter and N. J. Long, Dalton Trans., 2020, Advance Article , DOI: 10.1039/D0DT00332H

Social activity

Search articles by author

Spotlight

Advertisements