Mn-alginate gels as a novel system for controlled release of Mn2+ in manganese-enhanced MRI

Abstract

The aim of the present study was to test alginate gels of different compositions as a system for controlled release of manganese ions (Mn2+) for application in manganese‐enhanced MRI (MEMRI), in order to circumvent the challenge of achieving optimal MRI resolution without resorting to high, potentially cytotoxic doses of Mn2+. Elemental analysis and stability studies of Mn‐alginate revealed marked differences in ion binding capacity, rendering Mn/Ba‐alginate gels with high guluronic acid content most stable. The findings were corroborated by corresponding differences in the release rate of Mn2+ from alginate beads in vitro using T1‐weighted MRI. Furthermore, intravitreal (ivit) injection of Mn‐alginate beads yielded significant enhancement of the rat retina and retinal ganglion cell (RGC) axons 24 h post‐injection. Subsequent compartmental modelling and simulation of ivit Mn2+ transport and concentration revealed that application of slow release contrast agents can achieve a significant reduction of ivit Mn2+ concentration compared with bolus injection. This is followed by a concomitant increase in the availability of ivit Mn2+ for uptake by RGC, corresponding to significantly increased time constants. Our results provide proof‐of‐concept for the applicability of Mn‐alginate gels as a system for controlled release of Mn2+ for optimized MEMRI application.