title: 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 (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.
authors.affiliation: Department of Biotechnology, Norwegian University of Science and Technology, Trondheim, Norway. yrr.morch@ntnu.no
authors.forename: Yrr A
authors.initials: YA
authors.lastname: Mørch
authors.forename: Ioanna
authors.initials: I
authors.lastname: Sandvig
authors.forename: Oystein
authors.initials: O
authors.lastname: Olsen
authors.forename: Ivan
authors.initials: I
authors.lastname: Donati
authors.forename: Marte
authors.initials: M
authors.lastname: Thuen
authors.forename: Gudmund
authors.initials: G
authors.lastname: Skjåk-Braek
authors.forename: Olav
authors.initials: O
authors.lastname: Haraldseth
authors.forename: Christian
authors.initials: C
authors.lastname: Brekken
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002413:Cations, Divalent; D002942:Circular Dichroism; D003692:Delayed-Action Preparations; D005782:Gels / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese / Q000737:chemistry*; D051381:Rats; D013997:Time Factors; D014783:Viscosity
chemical_list: D000464:Alginates; D002413:Cations, Divalent; D003692:Delayed-Action Preparations; D005782:Gels; D006603:Hexuronic Acids; D008345:Manganese; D020723:Glucuronic Acid