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Magnetic Targeting of Nanometric Magnetic Fluid–loaded Liposomes to Specific Brain Intravascular Areas: A Dynamic Imaging Study in Mice¹

¹ From the Laboratoire Matière et Systèmes Complexes, CNRS UMR 7057, Université Paris 7-Denis Diderot, 140, rue de Lourmel, 75015 Paris, France (C.R., C.W., F.G.); Equipe Physico-Chimie des Systèmes Polyphasés, Chatenay-Malabry, France (M.S.M., S.L.); Centre de Recherche Cardiovasculaire Lariboisière, Paris, France (Y.T., A.T.D., E.P., J.S.); and Laboratoire des Liquides Ioniques et Interfaces Chargées, Paris, France (C.R., C.M.). Received May 25, 2006; revision requested July 26; revision received September 19; accepted October 26; final version accepted December 14. Supported by Institut National de la Santé et de la Recherche Medicale (INSERM), Ministère de l'Education Nationale de l'Enseignement Superieur et de la Recherche (ACI Nanosciences 145), and Direction Générale de l'Armement (DGA). Y.T. supported by INSERM. Address correspondence to F.G. (e-mail: floga{at}ccr.jussieu.fr).

Purpose: To prospectively determine, by using dynamic imaging, whether a magnet placed over a specific area of the mouse brain could target systemically administered rhodamine-labeled magnetic fluid–loaded liposomes (MFLs) to that brain region.

Materials and Methods: Experiments were performed with a French Ministry of Agriculture permit and regional ethics committee authorization. In seven anesthetized C57BL/6 mice, a closed cranial window was implanted above the left parieto-occipital cortex. A laser-scanning confocal fluorescence microscope (LSCFM) was used to track the intravenously injected rhodamine-labeled MFLs within this cortical area, through the cranial window. The MFLs were video monitored for 2 minutes every 15 minutes for 1 hour after injection. A magnet was placed on the cranial window implanted in four mice, while no magnet was placed in three (control) mice. After dynamic in vivo imaging, static in vivo imaging was performed with a different LSCFM. Ex vivo fluorescence histologic analysis was then performed. Paired Student t testing was used to compare the cerebral blood flow and two-dimensional flow values before and 1 hour after MFL injection. For image analysis, intergroup comparisons were performed by using an independent t test.

Results: In vivo video monitoring through the window revealed that the rhodamine-labeled MFLs accumulated in the mouse brain microvasculature exposed to the magnet—first within superficial brain venules and then within intracerebral venules—with no significant change in blood flow (P > .05). MFLs accumulated neither in the arterioles of the mice with a magnet nor in the arterioles of the control mice. Static in vivo imaging findings confirmed the microvascular localization of the rhodamine-labeled MFLs, and histologic findings specified their accumulation on the side of the magnet only.

Conclusion: Real-time in vivo imaging of rhodamine-labeled MFLs in the mouse brain cortex revealed that these nanosystems can be magnetically targeted, through microvessels, to selected brain areas.

Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/2442060912/DC1

© RSNA, 2007