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

• Published in: Contrast media and molecular imaging Vol. 7; no. 2; p. 265
• Main Authors: Mørch, Yrr A, Sandvig, Ioanna, Olsen, Oystein, Donati, Ivan, Thuen, Marte, Skjåk-Braek, Gudmund, Haraldseth, Olav, Brekken, Christian
• Format: Journal Article
• Language: English
• Published: England 01.03.2012
• Subjects: Alginates - chemistry; Animals; Cations, Divalent; Circular Dichroism; Delayed-Action Preparations; Gels - chemistry; Glucuronic Acid - chemistry; Hexuronic Acids - chemistry; Imaging, Three-Dimensional; Magnetic Resonance Imaging - methods; Manganese - chemistry; Rats; Time Factors; Viscosity
• ISSN: 1555-4317
• DOI: 10.1002/cmmi.493

The aim of the present study was to test alginate gels of different compositions as a system for controlled release of manganese ions (Mn(2+)) 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 Mn(2+). 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 Mn(2+) from alginate beads in vitro using T(1)-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 Mn(2+) transport and concentration revealed that application of slow release contrast agents can achieve a significant reduction of ivit Mn(2+) concentration compared with bolus injection. This is followed by a concomitant increase in the availability of ivit Mn(2+) 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 Mn(2+) for optimized MEMRI application.