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Iron Oxide Nanoparticle–labeled Rat Smooth Muscle Cells: Cardiac MR Imaging for Cell Graft Monitoring and Quantitation¹

¹ From the Laboratoire des Milieux Désordonnés et Hétérogènes (C.R., F.G.) and Laboratoire des Liquides Ioniques et Interfaces Chargées (J.R., J.N.P.), Université Pierre et Marie Curie, Paris, France; ERIT-M 0204 INSERM (F.P.B., J.P.L., D.L., J.F.D.) and U460 INSERM (J.B.M.), Universités Paris 7 et 13, INSERM Bldg, and Service de Radiologie (J.P.L.), Hôpital Bichat, 46 rue H. Huchard, 75877 Paris Cedex 18, France; Service de Radiologie, Université Paris 6, Hôpital Tenon, Paris, France (F.P.B., J.F.D.); and Centre de Recherches Chirurgicales, UFR de Médecine, Université Paris 12, Hôpital H. Mondor, Créteil, France (E.A.). Received December 18, 2003; revision requested February 20, 2004; final revision received June 22; accepted July 26. Supported by Institut National de la Santé et de la Recherche Médicale; Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche (ACI Technologies pour la Santé); Fondation Bettencourt-Schueller (Prix Coup d’Elan); Fondation de la Recherche Médicale; and Direction Générale de l’Armement. Address correspondence to J.F.D. (e-mail: jean-francois.deux@hmn.ap-hop-paris.fr).

PURPOSE: To perform a quantitative analysis of anionic maghemite nanoparticle–labeled cells in vitro and determine the effect of labeling on signal intensity at magnetic resonance (MR) imaging.

MATERIALS AND METHODS: The study was approved by the institutional animal care and use committee at Hôpital Bichat. In vitro cell proliferation, iron content per cell, and MR signal intensity of cells were measured in agarose phantoms for 0–14 days of culture after labeling of rat smooth muscle cells with anionic maghemite nanoparticles. Next, iron oxide–labeled smooth muscle cells were injected into healthy hearts and hearts with ischemic injury in seven live Fisher rats. Ex vivo MR imaging experiments in excised hearts 2 and 48 hours after injection were performed with a 1.5-T medical imaging system by using T2-weighted gradient-echo and spin-echo sequences. Histologic sections were obtained after MR imaging. Correlation analyses between division factor of iron load and cell amplification factor and between 1/T2 and number of labeled cells or number of days in culture were performed by using linear regression.

RESULTS: Viability of smooth muscle cells was not affected by magnetic labeling. Transmission electron micrographs of cells revealed the presence of iron oxide nanoparticles in vesicles up to day 14 of culture. Intracellular iron concentration decreased in parallel with cell division (r² = 0.99) and was correlated with MR signal intensity (r² = 0.95). T2*-weighted MR images of excised rat hearts showed hypointense signal in myocardium at 2 and 48 hours after local injection of labeled cells. Subsequent histologic staining evidenced iron oxide nanoparticles within cells and confirmed the presence of the original cells at 2 and 48 hours after implantation.

CONCLUSION: Magnetic labeling of smooth muscle cells with anionic maghemite nanoparticles allows detection of cells with MR imaging after local transplantation in the heart.

© RSNA, 2005

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