MnO-Labeled Cells: Positive Contrast Enhancement in MRI

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• 作者：Mathieu L茅tourneau ; M茅lanie Tremblay ; Luc Faucher ; Dario Rojas ; Pascale Chevallier ; Yves Gossuin ; Jean Lagueux ; Marc-Andr茅 Fortin
• 刊名：The Journal of Physical Chemistry B
• 出版年：2012
• 出版时间：November 8, 2012
• 年：2012
• 卷：116
• 期：44
• 页码：13228-13238
• 全文大小：543K
• 年卷期：v.116,no.44(November 8, 2012)
• ISSN：1520-5207

文摘

Manganese oxide (MnO) nanoparticles have been suggested as a promising 鈥減ositive鈥?MRI contrast agent for cellular and molecular studies. Mn-based contrast agents could enable T₁-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 T₁-weighted imaging due to high longitudinal relaxivities (r₁) and low r₂/r₁ ratios (USPMnO: r₁ = 3.4 卤 0.1 mM^鈥?s^鈥?, r₂/r₁ = 3.2; SPMnO: r₁ = 17.0 卤 0.5 mM^鈥?s^鈥?, r₂/r₁ = 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 Mn²⁺ 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 鈥減ositive鈥?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 T₁-weighted imaging sequences. This study confirms the potential of SPMnO and USPMnO to establish more quantitative cell tracking procedures with MRI.