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Magnetic Targeting of Magnetoliposomes to Solid Tumors with MR Imaging Monitoring in Mice: Feasibility¹

¹ From the Laboratoire Matière et Systèmes Complexes, Groupe Physique du Vivant, Université Paris 7, MSC, 140 rue de Lourmel, 75015 Paris, France (J.P.F., F.G., C.W., J.C.B.); Laboratoire de Recherche en Imagerie, Faculté de Médecine Necker, Paris, France (J.P.F., O.C.); Equipe Physico-Chimie des Systèmes Polyphasés, Faculté de Pharmacie, Chtenay-Malabry, France (M.S.M., S.L.); and Laboratoire des Liquides Ioniques et Interfaces Chargées, Université Paris 6, Paris, France (C.M.). Received December 13, 2004; revision requested February 7, 2005; revision received May 2; accepted June 3; final version accepted July 20. Supported by the French Ministry of Education and Research, Centre National de la Recherche Scientifique (ACI Nanoscience et Nanotechnologie NR145), and Institut National de la Santé et de la Recherche Médicale (Programme Interdisciplinaire Imagerie du Petit Animal). Address correspondence to J.P.F. (e-mail: fortin{at}ccr.jussieu.fr).

Purpose: To establish the feasibility of magnetoliposome tumor targeting with an extracorporeal magnet.

Materials and Methods: Animal experiments were performed in compliance with Institut National de la Santé Et de la Recherche Médicale animal protection guidelines and were approved by local government authorities. Magnetophoresis was used to measure the velocity of magnetoliposomes constituted of polyethylene glycol–lipids and anionic maghemite nanocrystals in a calibrated magnetic field in vitro. For in vivo studies, 38 male Swiss nude mice bearing a PC3 human prostate carcinoma tumor in each flank received an intravenous injection of magnetoliposomes (n = 27), saline (n = 9), or nonencapsulated superparamagnetic particles (n = 2) after a small magnet with a magnetic field of 0.3 T and a field gradient of 11 T/m was fixed to the skin above one tumor. The animals were examined at magnetic resonance (MR) imaging with eight different sequences, iron doses (13 mice), and magnet-application durations (12 mice). Their excised tumors were then stained with Perls Prussian blue and hematoxylin-eosin and were examined histologically. With use of the paired Student t test, signal intensity, tumor surface enhancement, and number of stained cells were compared between the control and magnet-exposed tumors to determine significant differences (P .01).

Results: The mean magnetoliposome velocity ranged from 10 to 40 µm/sec when the magnetic field equaled 0.13 T and the field gradient equaled 25 T/m. At T1-weighted three-dimensional spoiled gradient-echo MR imaging in vivo, the tumor exposed to the magnet showed strong negative enhancement, –52%, compared with the –7% enhancement of the other tumor. Maximal enhancement occurred after 3 hours of magnet application. After 24 hours of magnet application, intracapillary iron particle accumulation was observed in the targeted tumors only.

Conclusion: Magnetic targeting of sterically stabilized magnetoliposomes after they are intravenously injected is feasible in vivo.

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