title: Alginate-lanthanide microspheres for MRI-guided embolotherapy.
abstract: In cancer therapy, a promising treatment option to accomplish a high tumor-to-normal-tissue ratio is endovascular intervention with microsized particles, such as embolotherapy. In this study, alginate microspheres (ams) were prepared with the JetCutter technique, which is based on cutting a sodium alginate solution jet stream into small droplets of uniform size which are then cross-linked with different lanthanides or iron-III, resulting in microspheres of a predefined size which can be visualized by magnetic resonance imaging (MRI). The microspheres were investigated for their size and morphology (light microscopy and scanning electron microscopy analysis), cation content and MRI properties. The lanthanide-ams formulations, with a uniform size of 250 μm and a cation content between 0.72-0.94%, showed promising results for MR imaging. This was further demonstrated for Ho(3+)-cross-linked alginate microspheres (Ho(3+)-ams), the most potent microsphere formulation with respect to MR visualization, allowing single sphere detection and detailed microsphere distribution examination. Intravascular infusion of Ho(3+)-ams by catherization of ex vivo rabbit and porcine liver tissue and assessment of the procedure with MRI clearly showed accumulation and subsequently embolization of the targeted vessels, allowing accurate monitoring of the microsphere biodistribution throughout the tissue. Therefore, the different alginate-lanthanide microsphere formulations developed in this study show great potential for utilization as image-guided embolotherapy agents.
authors.affiliation: Department of Radiology and Nuclear Medicine, University Medical Center, Utrecht, The Netherlands. C.Oerlemans@umcutrecht.nl
authors.forename: Chris
authors.initials: C
authors.lastname: Oerlemans
authors.forename: Peter R
authors.initials: PR
authors.lastname: Seevinck
authors.forename: Gerrit H
authors.initials: GH
authors.lastname: van de Maat
authors.forename: Hassan
authors.initials: H
authors.lastname: Boulkhrif
authors.forename: Chris J G
authors.initials: CJ
authors.lastname: Bakker
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: J Frank W
authors.initials: JF
authors.lastname: Nijsen
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D004621:Embolization, Therapeutic / Q000379:methods*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D028581:Lanthanoid Series Elements / Q000737:chemistry*; D008099:Liver; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011817:Rabbits; D013552:Swine
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D028581:Lanthanoid Series Elements; D020723:Glucuronic Acid