Pharmaceutical Research

, Volume 27, Issue 9, pp 1884–1892

Dextran Gadolinium Complexes as Contrast Agents for Magnetic Resonance Imaging to Sentinel Lymph Nodes

  • Guo-Ping Yan
  • Wei Xu
  • Lian Yang
  • Liang Li
  • Fan Liu
  • Qing-Zhong Guo
Research Paper



The aim was to investigate three dextran gadolinium complexes Dextran-DTPA-Gd as the potential MRI contrast agents in lymphatic system.


Three dextran gadolinium complexes Dextran-DTPA-Gd containing differing amounts of Gd-DTPA were synthesized by the incorporation of Gd-DTPA to the hydroxyl groups of dextran. These dextran ligands and gadolinium complexes were characterized, and their properties in vitro and in vivo were also evaluated.


Dextran-DTPA-Gd demonstrated obviously higher relaxation effectiveness than that of Gd-DTPA. The result of in vitro cytotoxicity assay showed that these macromolecular ligands and their corresponding gadolinium complexes had low cytotoxicity to HeLa cells. Dextran-DTPA-Gd greatly enhanced the contrast of MR images of normal politeal lymph nodes and reactive hyperplasia of politeal lymph nodes in rabbits and provided prolonged duration in lymphatic system with lower injection doses than that of Gd-DTPA. However, Dextran-DTPA-Gd displayed low signal enhancements in MR images of politeal lymph nodes with VX2 carcinoma in rabbits during the detection time.


These dextran gadolinium complexes Dextran-DTPA-Gd can be taken up selectively by lymphatic system and showed the potential as MRI contrast agents in lymphatic system.


magnetic resonance imaging (MRI) contrast agents gadolinium complexes dextran politeal lymph nodes 


  1. 1.
    Lauterbur PC. Image formation by induced local interactions: examples employing nuclear magnetic resonance. Nature. 1973;242:190–1.CrossRefGoogle Scholar
  2. 2.
    Lauffer RB. Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design. Chem Rev. 1987;87:901–27.CrossRefGoogle Scholar
  3. 3.
    Caravan P, Ellison JJ, Mcmurry TJ, Lauffer RB. Gadolinium (III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev. 1999;99:2293–352.CrossRefPubMedGoogle Scholar
  4. 4.
    Yan GP, Robinsonand L, Hogg P. Magnetic resonance imaging contrast agents: overview and perspectives. Radiography. 2007;13:e5–19.CrossRefGoogle Scholar
  5. 5.
    Yan GP, Zhuo RX. Research progress of magnetic resonance imaging contrast agents. Chin Sci Bull. 2001;46(15):1233–7.CrossRefGoogle Scholar
  6. 6.
    Yan GP, Zhang JY, Zhou JX, Bottle SE, Yu XH, Wu JY, Li L. Targeted contrast agents for molecular imaging in magnetic resonance imaging (MRI). Recent Advances of Bioconjugate Chemistry in Molecular Imaging, (ISBN 978-81-0210-7), Chen XY. Ed., 2008;371–98, Chapter 19, Research Signpost, Kerala, India.Google Scholar
  7. 7.
    Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, van de Kaa CH, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med. 2003;348(25):2491–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Swartz MA. The physiology of the lymphatic system. Adv Drug Deliv Rev. 2001;50(1-2):3–20.CrossRefPubMedGoogle Scholar
  9. 9.
    Liu ZY. Lymphatic basic theory research and clinical application. Beijing: Science; 2003. p. 132–41. ISBN ISBN 7-03-009996-6.Google Scholar
  10. 10.
    Fujimoto Y, Okuhata Y, Tyngi S, Namba Y, Oku N. Magnetic resonance lymphography of profundus lymph nodes with liposomal gadolinium-diethylenetriamine pentaacetic acid. Biol Pharm Bull. 2000;23:97–100.PubMedGoogle Scholar
  11. 11.
    Harika L, Weissleder R, Poss K, Zimmer C, Papisov MI, Brady TJ. MR lymphography with a lymphotropic T1-type MR contrast agent: Gd-DTPA-PGM. Magn Reson Med. 1995;33:88–92.CrossRefPubMedGoogle Scholar
  12. 12.
    Misselwitz B, Platzek J, Raduchel B, Oellinger JJ, Weinmann HJ. Gadofluorine 8: initial experience with a new contrast medium for interstitial MR lymphography. Magn Reson Mater Phy. 1999;8:190–95.Google Scholar
  13. 13.
    Staatz G, Spuntrup E, Buecker A, Misselwitz B, Gunther RW. T1-weighted MR-lymphography after intramammary administration of Gadomer-17 in pigs. Rofo-Fortschr Rontg. 2002;174:29–32.CrossRefGoogle Scholar
  14. 14.
    Kobayashi H, Kawamoto S, Star RA, Waldmann TA, Tagaya Y, Brechbiel MW. Micro-magnetic resonance lymphangiography in mice using a novel dendrimer-based magnetic resonance imaging contrast agent. Cancer Res. 2003;63:271–76.PubMedGoogle Scholar
  15. 15.
    Elste V, Wagner S, Taupitz M, Pfefferer D, Kresse M, Hamm B, et al. Magnetic resonance lymphography in rats: effects of muscular activity and hyperthermia on the lymph node uptake of intravenously injected superparamagnetic iron oxide particles. Acad Radiol. 1996;3:660–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Hamm B, Taupitz M, Hussmann P, Wagner S, Wolf KJ. MR lymphography with iron oxide particles: dose-response studies and pulse sequence optimization in rabbits. Am J Roentgenol. 1992;158:183–90.Google Scholar
  17. 17.
    Rety F, Clement O, Siauve N, Cuenod CA, Carnot F, Sich M, et al. MR lymphography using iron oxide nanoparticles in rats: pharmacokinetics in the lymphatic system after intravenous injection. J Magn Reson Imaging. 2000;12:734–39.CrossRefPubMedGoogle Scholar
  18. 18.
    Wen J, Zhuo RX, Wang L. Aromatic DTPA-Bis(amide) gadolinium complexes as hepatobiliary contrast agents for magnetic resonance imaging. Chin J Magn Reson. 1998;15(3):217–21.Google Scholar
  19. 19.
    Van Beer BE, Gallez B, Pringot J. Contrast-enhanced MR imaging of the liver. Radiology. 1997;203:297–306.Google Scholar
  20. 20.
    Yan GP, Liu ML, Li LY. Studies on polyaspartamide gadolinium complexes containing sulfadiazine groups as MRI contrast agents. Bioconjugate Chem. 2005;16:967–71.CrossRefGoogle Scholar
  21. 21.
    Yan GP, Peng L, Jian SQ, Li L, Bottle SE. Spin probes for electron paramagnetic resonance imaging. Chin Sci Bull. 2008;53(24):3777–89.CrossRefGoogle Scholar
  22. 22.
    Yan GP, Bischa D, Bottle SE. Synthesis and properties of novel porphyrin spin probes containing isoindoline nitroxides. Free Radical Bio Med. 2007;43(1):111–6.CrossRefGoogle Scholar
  23. 23.
    Yan GP, Hu B, Liu ML, Li LY. Synthesis and evaluation of gadolinium complexes based on PAMAM as MRI contrast agents. J Pharm Pharmacol. 2005;57(3):351–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Yan GP, Liu ML, Li LY. Studies on polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents. Radiography. 2005;11:117–22.CrossRefGoogle Scholar
  25. 25.
    Yan GP, Bottle SE, Zhuo RX, Wei L, Liu ML, Li LY. Evaluation on dendritic gadolinium complexes as MRI contrast agents. J Bioact Compatible Polym. 2004;19(6):453–65.CrossRefGoogle Scholar
  26. 26.
    Yan GP, Zheng CY, Cao W, Wei L, Zhang YX, Zhuo RX. Synthesis and preliminary evaluation of gadolinium complexes containing sulfonamide groups as potential MRI contrast agents. Radiography. 2003;9:35–41.CrossRefGoogle Scholar
  27. 27.
    Yan GP, Zhuo RX, Zhang X, Liu ML, Li LY, Ye ZH. Hepatic targeting macromolecular MRI contrast agents. Polym Int. 2002;51:892–8.CrossRefGoogle Scholar
  28. 28.
    Yan GP, Zhuo RX, Yang YH, Liu ML, Li LY, Ye ZH. Tumor-selective macromolecular MRI contrast agents. J Bioact Compatible Polym. 2002;17(2):139–51.CrossRefGoogle Scholar
  29. 29.
    Yan GP, Zhuo RX, Xu MY, Tang YF, Li LY. Liver-targeting macromolecular MRI contrast agents. Sci China Ser B. 2001;44(4):344–52.CrossRefGoogle Scholar
  30. 30.
    Yan GP, Wang XY, Mei LL. Vitamin B6 as liver-targeting group in drug delivery. In: Elliot CM, editor. Vitamin B: new research. Hauppauge: Nova Science; 2008. p. 153–74.Google Scholar
  31. 31.
    Rinaudo M. Characterization and properties of some polysaccharides used as biomaterials. Macromol Symp. 2007;245-246:549–57.CrossRefGoogle Scholar
  32. 32.
    Rinaudo M. Main properties and current applicationsof some polysaccharides as biomaterials. Polym Int. 2008;57(3):397–430.CrossRefGoogle Scholar
  33. 33.
    Suh JKF, Matthew HWT. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials. 2000;21(24):2589–98.CrossRefPubMedGoogle Scholar
  34. 34.
    Shi FQ. How to copy the disease model of animals. Yi Xue Dong Wu Shi Yan Fang Fa, 1990;226–232, Chapter 4, RenMing WeiSheng Press, Bejing, China.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Guo-Ping Yan
    • 1
  • Wei Xu
    • 1
  • Lian Yang
    • 2
  • Liang Li
    • 1
  • Fan Liu
    • 1
  • Qing-Zhong Guo
    • 1
  1. 1.School of Material Science and EngineeringWuhan Institute of TechnologyWuhanChina
  2. 2.Center for Magnetic Resonance Imaging of Union Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations