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Published online before print February 27, 2004, 10.1148/radiol.2311021559
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Glucose-Receptor MR Imaging of Tumors: Study in Mice with PEGylated Paramagnetic Niosomes1

Alain Luciani, MD, Jean-Christophe Olivier, PharmD, PhD, Olivier Clement, MD, PhD, Nathalie Siauve, MD, PhD, Pierre-Yves Brillet, MD, Bertrand Bessoud, MD, Florence Gazeau, PhD, Ijeoma F. Uchegbu, PhD, Edmond Kahn, PhD, Guy Frija, MD and Charles A. Cuenod, MD, PhD

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).



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  		Figure 1. Schematic representation of a glycosylated PEG 4400 niosome. NPG radicals (glucose conjugates) are included in the membrane of the vesicle. Gadobenate dimeglumine is entrapped within the vesicle. Span 60 is the trade name for sorbitan monostearate; Solulan C-24, trade name for a mixture of cholesteryl poly-24-oxyethylene ether and cetyl poly-24-oxyethylene ether; Brij 700, trade name for stearyl poly-100-oxyethylene ether.

 


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  		Figure 2. Graphs show tumor ({blacktriangleup}), liver ({diamondsuit}), brain (x), and muscle ({bullet}) enhancement (mean ± standard error of the mean) after contrast agent injection. A, Nonconjugated niosomes. B, Glycosylated niosomes. C, PEG 4400 niosomes. D, Glycosylated PEG 4400 niosomes. Predominant tumor enhancement is demonstrated 24 hours after glycosylated PEG 4400 niosome injection.

 


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  		Figure 3. Graphs show RI-to-time profiles (mean ± standard error of the mean) after injection of each contrast agent. A, Tumor. B, Liver. C, Brain. Highest tumor RI is observed 24 hours after glycosylated PEG 4400 niosome injection ({blacktriangleup}); highest liver RI is observed after gadobenate meglumine injection (x). In brain, RI-to-time profiles show a regular increase after glycosylated niosome ({blacksquare}) and glycosylated PEG 4400 niosome injection. {diamondsuit} = nonconjugated niosomes, {blacktriangledown} = PEG 4400 niosomes.

 


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  		Figure 4a. Transverse spin-echo T1-weighted MR images (500/10; section thickness, 3 mm) in two mice with xenograft PC3 tumors (arrowheads) 24 hours after injection of contrast agents. (a) Saline solution. (b) Glycosylated PEG 4400 niosomes. Image shows increased tumor RI and tumor-to-muscle CNR, with liver (Li) and gallbladder (Gb) enhancement. Lu = lung, m = muscle, * = heart.

 


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  		Figure 4b. Transverse spin-echo T1-weighted MR images (500/10; section thickness, 3 mm) in two mice with xenograft PC3 tumors (arrowheads) 24 hours after injection of contrast agents. (a) Saline solution. (b) Glycosylated PEG 4400 niosomes. Image shows increased tumor RI and tumor-to-muscle CNR, with liver (Li) and gallbladder (Gb) enhancement. Lu = lung, m = muscle, * = heart.

 




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