Skip to main content
Log in

Relaxivity of liposomal paramagnetic MRI contrast agents

  • Published:
Magnetic Resonance Materials in Physics, Biology and Medicine Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. 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

    PubMed  Google Scholar 

  2. Moghimi SM, Hunter AC, Murray JC (2001) Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev 53:283–318

    PubMed  Google Scholar 

  3. Crommelin DJ, Storm G (2003) Liposomes: from the bench to the bed. J Liposome Res 13:33–36

    Article  PubMed  Google Scholar 

  4. Weissleder R, Mahmood U (2001) Molecular imaging. Radiology 219:316–333

    PubMed  Google Scholar 

  5. 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

    Article  PubMed  Google Scholar 

  6. Nunn AD, Linder KE, Tweedle MF (1997) Can receptors be imaged with MRI agents? Q J Nucl Med 41:155–162

    PubMed  Google Scholar 

  7. 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

    Article  PubMed  Google Scholar 

  8. 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

    Article  PubMed  Google Scholar 

  9. 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

    Article  Google Scholar 

  10. 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

    Article  PubMed  Google Scholar 

  11. 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

    PubMed  Google Scholar 

  12. 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

    PubMed  Google Scholar 

  13. Frederik PM, Hubert DHW (2005) Cryo-electron microscopy of liposomes. In: Duzgunes N (Ed.) Liposomes, part E. Academic, New York London

  14. 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

    Article  Google Scholar 

  15. 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

    Article  Google Scholar 

  16. Dekker M (1993) Phospholipids Handbook. Marcel Dekker Inc., New York 1993

  17. 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

    Article  PubMed  Google Scholar 

  18. 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

    Article  PubMed  Google Scholar 

  19. 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

  20. 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

  21. 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

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to G.J. Strijkers.

Rights and permissions

Reprints 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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10334-005-0111-y

Keywords

Navigation