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Experimental Studies |
1 From the Radiology Department, Hôpital Européen Georges Pompidou, INSERM U494, LRI, Faculté Necker, 20 Rue Leblanc, 75015 Paris, France (A.L., O.C., N.S., P.Y.B., B.B., E.K., G.F., C.A.C.); Laboratoire de Pharmacie Galénique et Biopharmacie, Equipe émergente "Médicaments anti-infectieux et barrière Hémato-encéphalique," Faculté de Médecine et de Pharmacie, Poitiers, France (J.C.O.); CNRS UMR 7603, Laboratoire des Milieux Désordonnés Hétérogènes et de Pharmacologie Clinique LMDH, Faculté Paris VI-VII, France (F.G.); and Department of Pharmaceutical Sciences, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, Scotland (I.F.U.). From the 2002 RSNA scientific assembly. Received November 25, 2002; revision requested February 20, 2003; revision received May 29; accepted June 30. Address correspondence to C.A.C. (e-mail: ca@cuenod.net).
PURPOSE: To evaluate a magnetic resonance (MR) imaging contrast agent for tumor detection based on paramagnetic nonionic vesicles (niosomes) bearing polyethylene glycol (PEG) and glucose conjugates for the targeting of overexpressed glucose receptors.
MATERIALS AND METHODS: Four gadobenate dimeglumine–loaded niosome preparations including nonconjugated niosomes, niosomes bearing glucose conjugates (N-palmitoyl glucosamine [NPG]), niosomes bearing PEG 4400, and niosomes bearing both PEG and NPG were tested. In vitro cellular uptake was measured at electron paramagnetic resonance (EPR) after incubation with human prostate carcinoma, PC3, cells. In vivo distribution was studied at MR imaging 6, 12, and 24 hours after injection, with assessment of tumor, brain, liver, and muscle signal intensity (SI) in 49 mice bearing PC3 cells. Efficiency of targeted contrast agents was assessed with tumor-to-muscle contrast-to-noise ratio (CNR). Testing for differences was performed with analysis of variance followed by a posteriori Fisher test.
RESULTS: In vitro, gadolinium could be detected at EPR only in cell pellets incubated with niosomes bearing glucose conjugates or niosomes bearing both glucose conjugates and PEG (4.9·10-15 and 4.5·10-15 mol gadolinium per PC3 cell). In vivo, marked predominant tumor enhancement was demonstrated 24 hours after injection of glycosylated PEG niosomes (P < .01); no significant differences were observed following injection of nonconjugated niosomes, glycosylated niosomes, or PEG 4400 niosomes. Twenty-four hours after injection, sole presence of NPG or PEG 4400 on the surface of the niosome led to higher tumor-to-muscle CNR than that observed after injection of nonconjugated niosomes (CNR of 3.3 ± 0.7 [SD], 3.4 ± 2.2, and 0 ± 1.9). Combination of NPG and PEG led to even higher tumor-to-muscle CNR (6.3 ± 2.2).
CONCLUSION: Combination of PEG and glucose conjugates on the surface of niosomes significantly improved tumor targeting of an encapsulated paramagnetic agent assessed with MR imaging in a human carcinoma xenograft model.
© RSNA, 2004
Index terms: Animals • Glucose • Liposomes • Magnetic resonance (MR), contrast media • Neoplasms, experimental studies
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