Abstract
Nuclear magnetic relaxation dispersion (NMRD) profiles of unilamellar DPPC liposomes incorporating Gd-DTPA-bisamides with alkyl chains of 12 to 18 C atoms in their external and internal layers were recorded in order to study the influence that the chain length and structure of Gd-bisamides incorporated in the liposomal membrane have on their proton relaxivity. The NMRD profiles recorded at 310 K show that the relaxivity reaches a minimum value when the carbon chain lengths of the phospholipid and of the Gd complex match and is at a maximum in the presence of a carbon–carbon double bond. For these DPPC paramagnetic liposomes, the longer the aliphatic chains of the complex, the larger will be its immobilization in the membrane. In addition, the presence of an unsaturated carbon–carbon bond in the alkyl chain of the Gd complex induces an increase of its mobility and of its water exchange rate with, as a result, a much greater efficiency as an MRI contrast agent.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Barge A, Cravotto G, Gianolio E, Fedeli F (2006) How to determine free Gd and free ligand in solution of Gd chelates. A technical note. Contrast Media Mol Imaging 1:184–188
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(3):669–672
Bloembergen N (1957) Proton relaxation times in paramagnetic solutions. J Chem Phys 27:572–573
Cacheris WP, Grabiak RC, Lee AC, Richard TJ, Goodin TH, Kaufman RJ (1994) Emulsions of lipophilic paramagnetic complexes as MRI contrast media, Proceedings of the 4th special topic seminar of the European Magnetic Resonance Forum, Rinck PA, Muller RN (eds) Germany, pp 37–51
Cattel L, Ceruti M, Dosio F (2003) From conventional to stealth liposomes: a new frontier in cancer chemotherapy. Tumori 89(3):237–249
Fossheim S, Fahlvik AK, Klaveness J, Muller RN (1999) Paramagnetic liposomes as MRI contrast agents: influence of liposomal physicochemical properties on the in vitro relaxivity. Magn Reson Imaging 17:83–89
Freed JH (1978) Dynamic effects of pair correlation functions on spin relaxation by translational diffusion in liquids. II. Finite jumps and independent T1 processes. J Chem Phys 68:4034–4037
Freyschmidt-Paul P, Happle R, McElwee KJ, Hoffmann R (2003) Alopecia areata: treatment of today and tomorrow. J Investig Dermatol Symp Proc 8(1):12–17
Johnston SR (2004) Ovarian cancer: review of the National Institute for Clinical Excellence (NICE) guidance recommendations. Cancer Invest 22(5):730–742
Kedei N, Lundberg DJ, Toth A, Welburn P, Garfield SH, Blumberg PM (2004) Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res 64(9):3243–3255
Kimpe K, Parac-Vogt TN, Laurent S, Piérart C, Vander Elst L, Muller RN, Binnemans K (2003) Potential MRI contrast agents based on micellar incorporation of amphiphilic bis(alkylamide) derivatives of [(Gd-DTPA)(H2O)]2− Eur J Inorg Chem 3021–3027
Konduri KS, Nandedkar S, Duzgunes N, Suzara V, Artwohl J, Bunte R, Gangadharam PR (2003) Efficacy of liposomal budesonide in experimental asthma. J Allergy Clin Immunol 111(2):321–327
Krugner-Higby L, Smith L, Clark M, Heath TD, Dahly E, Schiffman B, Hubbard-VanStelle S, Ney D, Wendland A (2003) Liposome-encapsulated oxymorphone hydrochloride provides prolonged relief of postsurgical visceral pain in rats. Comp Med 53(3):270–279
Lasic DD (1993) Liposomes from physics to applications. Elsevier, Amsterdam
Lattuada L, Lux G (2003) Synthesis of Gd-DTPA-cholesterol: a new lipophilic gadolinium complex as a potential MRI contrast agent. Tetrahedron Lett 44(20):3893–3895
Laurent S, Vander Elst L, Thirifays C, Muller RN (2008) Paramagnetic liposomes: inner versus outer membrane relaxivity of DPPC liposomes incorporating lipophilic gadolinium complexes. Langmuir (in press)
Leclercq F, Cohen-Ohana M, Mignet N, Sbarbati A, Herscovici J, Scherman D, Byk G (2003) Design, synthesis, and evaluation of gadolinium cationic lipids as tools for biodistribution studies of gene delivery complexes. Bioconjugate Chem. 14:112–119
Lokling KE, Skurtveit R, Bjornerud A, Fossheim SL (2004a) Novel pH-sensitive paramagnetic liposomes with improved MR properties. Magn Reson Med 51(4):688–696
Lokling KE, Fossheim SL, Klaveness J, Skurtveit R (2004b) Biodistribution of pH-responsive liposomes for MRI and a novel approach to improve the pH-responsiveness. J Control Release 98(1):87–95
Shoji Y, Nakashima H (2004) Current status of delivery systems to improve target efficacy of oligonucleotides. Curr Pharm Des 10(7):785–796
Solomon I (1955) Relaxation processes in a system of two spins. Phys Rev 99:559–565
Strijkers GJ, Mulder WJM, Van Heeswijk RB, Frederik PM, Bosmans P, Magusin PMM, Nicolay K (2005) Relaxivity of liposomal paramagnetic MRI contrast agents. Magn Reson Mater Phys 18:186–192
Torchilin VP (1996) Liposomes as delivery agents for medical imaging. Mol Med Today 6:242–249
Torchilin VP (1997) Surface-modified liposomes in gamma- and MR-imaging. Adv Drug Del 301–313
Trubetskoy VS, Frank-Kamenetsky MD, Whiteman KR, Wolf GL, Torchilin VP (1996) Stable polymeric micelles: lymphangiographic contrast media for gamma scintigraphy and magnetic resonance imaging. Acad Radiol 3:232–238
Acknowledgments
The authors thank Mrs. Patricia de Francisco for her help in preparing the manuscript. This work was supported by the FNRS and the ARC Program 00/05–258 of the French Community of Belgium. The support and sponsorship of the COST Actions D18 “Lanthanide Chemistry for Diagnosis and Therapy” and D38 “Metal-based Systems for Molecular Imaging Applications” and of the EMIL NoE of the FP6 of the EC are kindly acknowledged.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Laurent, S., Vander Elst, L., Thirifays, C. et al. Relaxivities of paramagnetic liposomes: on the importance of the chain type and the length of the amphiphilic complex . Eur Biophys J 37, 1007–1014 (2008). https://doi.org/10.1007/s00249-008-0331-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00249-008-0331-y