title: MnO-labeled cells: positive contrast enhancement in MRI.
abstract: Manganese oxide (MnO) nanoparticles have been suggested as a promising "positive" MRI contrast agent for cellular and molecular studies. Mn-based contrast agents could enable T(1)-weighted quantitative cell tracking procedures in vivo based on signal enhancement. In this study, ultrasmall MnO particles were synthesized and coated with thiolated molecules (DMSA) and polyethylene glycol (PEG) to allow enhanced cell labeling properties and colloidal stability. This coating allowed the fabrication of individual ultrasmall nanoparticles of MnO (USPMnO) as well as of nanoaggregates of the same material (SPMnO). Particle size was measured by TEM and DLS. Physico-chemical properties were characterized by XPS and FTIR. The relaxometric properties of these aqueous suspensions were measured at various magnetic fields. The suspensions provided strong positive contrast enhancement in T(1)-weighted imaging due to high longitudinal relaxivities (r(1)) and low r(2)/r(1) ratios (USPMnO: r(1) = 3.4 ± 0.1 mM(-1)s(-1), r(2)/r(1) = 3.2; SPMnO: r(1) = 17.0 ± 0.5 mM(-1)s(-1), r(2)/r(1) = 4.0, at 1.41T). HT-1080 cancer cells incubated with the contrast agents were clearly visualized in MRI for Mn contents >1.1 pg Mn/cell. The viability of cells was not affected, contrarily to cells labeled with an equivalent concentration of Mn(2+) ions. A higher signal per cell was found for SPMnO-labeled compared with USPMnO-labeled cells, due to the higher relaxometric properties of the agglomerates. As a result, the "positive" signal enhancement effect is not significantly affected upon agglomeration of MnO particles in endosomes. This is a major requirement in the development of reliable cell tracking procedures using T(1)-weighted imaging sequences. This study confirms the potential of SPMnO and USPMnO to establish more quantitative cell tracking procedures with MRI.
authors.affiliation: Axe métabolisme, santé vasculaire et rénale, Centre de recherche du Centre hospitalier universitaire de Québec (AMSVR-CRCHUQ), 10 rue de l'Espinay, Québec, QC G1L 3L5, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Létourneau
authors.forename: Mélanie
authors.initials: M
authors.lastname: Tremblay
authors.forename: Luc
authors.initials: L
authors.lastname: Faucher
authors.forename: Dario
authors.initials: D
authors.lastname: Rojas
authors.forename: Pascale
authors.initials: P
authors.lastname: Chevallier
authors.forename: Yves
authors.initials: Y
authors.lastname: Gossuin
authors.forename: Jean
authors.initials: J
authors.lastname: Lagueux
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Fortin
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008279:Magnetic Resonance Imaging; D017895:Manganese Compounds / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D046529:Microscopy, Electron, Transmission; D010087:Oxides / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D003287:Contrast Media; D017895:Manganese Compounds; D010087:Oxides; D013438:Sulfhydryl Compounds; D011092:Polyethylene Glycols; C027424:manganese oxide