Manganese-enhanced MRI: Comparison of agents in the rat pancreas

Abstract

Mangafodipir was approved for use as an MRI contrast agent in the late 1990s for liver and pancreas imaging but it was removed from the European market for commercial reasons in 2012. Previously, preliminary work in mice and in diabetic patients showed that Mn2+ ions could be used as a contrast agent to monitor the function of insulin-producing β-cells by acting as a calcium analogue. Clinical translation of this work was hampered by a lack of available Mn contrast agents, but both mangafodipir and Mn gluconate are currently being used in clinical trials.As a first step towards using Mn in diabetic patients to monitor treatment or disease progression, we imaged the pancreas of healthy rats using mangafodipir, Mn gluconate and Mn chloride (as a control). The hypothesis was that Mn gluconate produces pancreatic enhancement similar to that seen previously with mangafodipir and Mn chloride, with greater enhancement following glucose challenge vs saline challenge. 18 Wistar rats were imaged at 7 T and normalised plateau pancreatic enhancement over baseline was compared for saline vs glucose challenge, calculated from a sigmoid fit to the enhancement curve. For saline vs glucose challenge, mean increases in plateau height ± sd were: 22 ± 18% for Mn chloride, 31 ± 29% for mangafodipir and 41 ± 17% for Mn gluconate. A paired t-test indicated that enhancement was greater for glucose vs saline (p=0.01) and that there was no significant difference in the percentage enhancement between any of the compounds (p>0.2). In conclusion, all three contrast agents produced similar enhancement, with greater plateau height under glucose challenge vs saline challenge. Mangafodipir and Mn gluconate show potential for translation into a clinical study investigating beta cell imaging of the pancreas in type 1 diabetes mellitus and type 2 diabetes.

Keywords

• Manganese
• Diabetes
• Pancreas
• β-cells
• Pancreatic islets