Abstract
Paramagnetic liposomes, spherical particles formed by a lipid bilayer, are able to accommodate a high payload of Gd-containing lipid and therefore can serve as a highly potent magnetic resonance imaging contrast agent. In this paper the relaxation properties of paramagnetic liposomes were studied as a function of composition, temperature and magnetic field strength. The pegylated liposomes with a diameter of approximately 100 nm were designed for favorable pharmacokinetic properties in vivo. The proton relaxivity, i.e. the T1 relaxation rate per mmol of Gd(III) ions, of liposomes with unsaturated DOPC phospholipids was higher than those with saturated DSPC lipids. Addition of cholesterol was essential to obtain monodisperse liposomes and led to a further, although smaller, increase of the relaxivity. Nuclear magnetic relaxation dispersion measurements showed that the relaxivity was limited by water exchange. These results show that these paramagnetic liposomes are very effective contrast agents, making them excellent candidates for many applications in magnetic resonance imaging.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Drummond DC, Meyer O, Hong K, Kirpotin DB, Papahadjopoulos D (1999) Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev 51:691–743
Moghimi SM, Hunter AC, Murray JC (2001) Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 53:283–318
Crommelin DJ, Storm G (2003) Liposomes: from the bench to the bed. J Liposome Res 13:33–36
Weissleder R, Mahmood U (2001) Molecular imaging. Radiology 219:316–333
Mulder WJ, Strijkers GJ, Griffioen AW, van Bloois L, Molema G, Storm G, Koning GA, Nicolay K (2004) A liposomal system for contrast-enhanced magnetic resonance imaging of molecular targets. Bioconjug Chem 15:799–806
Nunn AD, Linder KE, Tweedle MF (1997) Can receptors be imaged with MRI agents? Q J Nucl Med 41:155–162
Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KC (1998) Detection of tumor angiogenesis in vivo by αVβ 3-targeted magnetic resonance imaging. Nat Med 4:623–626
Morawski AM, Winter PM, Crowder KC, Caruthers SD, Fuhrhop RW, Scott MJ, Robertson JD, Abendschein DR, Lanza GM, Wickline SA (2004) Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI. Magn Reson Med 51:480–486
Alhaique F, Bertini I, Fragai M, Carafa M, Luchinat C, Parigi G (2002) Solvent H-1 NMRD study of biotinylated paramagnetic liposomes containing Gd-bis-SDA-DTPA or Gd-DMPE-DTPA. Inorg Chim Acta 331:151–157
Glogard C, Stensrud G, Hovland R, Fossheim SL, Klaveness J (2002) Liposomes as carriers of amphiphilic gadolinium chelates: the effect of membrane composition on incorporation efficacy and in vitro relaxivity. Int J Pharm 233:131–140
Tilcock C, Ahkong QF, Koenig SH, Brown RD, III, Davis M, Kabalka G (1992) The design of liposomal paramagnetic MR agents: effect of vesicle size upon the relaxivity of surface-incorporated lipophilic chelates. Magn Reson Med 27:44–51
Allen TM, Hansen C, Martin F, Redemann C, Yau-Young A (1991) Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim Biophys Acta 1066:29–36
Frederik PM, Hubert DHW (2005) Cryo-electron microscopy of liposomes. In: Duzgunes N (Ed.) Liposomes, part E. Academic, New York London
Bertini I, Kowalewski J, Luchinat C, Nilsson T, Parigi G (1999) Nuclear spin relaxation in paramagnetic complexes of S=1: Electron spin relaxation effects. J Chem Phys 111:5795–5807
Kruk D, Nilsson T, Kowalewski J (2001) Nuclear spin relaxation in paramagnetic systems with zero-field splitting and arbitrary electron spin. Phys Chem Chem Phys 3:4907–4917
Dekker M (1993) Phospholipids Handbook. Marcel Dekker Inc., New York 1993
Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev 99:2293–2352
Bertini I, Bianchini F, Calorini L, Colagrande S, Fragai M, Franchi A, Gallo O, Gavazzi C, Luchinat C (2004) Persistent contrast enhancement by sterically stabilized paramagnetic liposomes in murine melanoma. Magn Reson Med 52:669–672
Mulder, WJ, Strijkers, GJ, Habets, JW, van der Schaft, DW, Storm, G, Koning, GA, Griffioen, AW, Nicolay, K (2005) Tumor vasculature labeling by αvβ 3-targeted liposomes. A combined MRI and fluorescence microscopy study. Proceedings of the 13th ISMRM Scientific Meeting. Miami, USA
van Tilborg, GA, Strijkers, GJ, Mulder, WJ, Reutelingsperger, CP, Nicolay, K (2005) AnnexinV-functionalized multimodal liposomes as contrast agents for apoptotic cells. Proceedings of the 13th ISMRM Scientific Meeting. Miami, USA
Mulder, WJ, Strijkers, GJ, Habets, JW, Koning, GA, Lutgens, E, Douma, K, van Zandvoort, MA, Slaaf, DW, Nicolay, K (2005) Detection of intimal thickening by contrast-enhanced MRI using paramagnetic liposomes. Proceedings of the 13th ISMRM Scientific Meeting. Miami, USA
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Strijkers, G., Mulder, W., van Heeswijk, R. et al. Relaxivity of liposomal paramagnetic MRI contrast agents. MAGMA 18, 186–192 (2005). https://doi.org/10.1007/s10334-005-0111-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10334-005-0111-y