Advertisement

Proteoglycans pp 183-198 | Cite as

In Vivo Scintigraphic Imaging of Proteoglycans

  • Elisabeth Miot-NoiraultEmail author
  • Aurélien Vidal
  • Philippe Auzeloux
  • Caroline Peyrode
  • Jean-Claude Madelmont
  • Jean-Michel Chezal
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 836)

Abstract

In this chapter, we present the methods developed in our lab for the scintigraphic imaging and direct quantitative evaluation of proteoglycan (PG) distribution in vivo. These methods relate to (1) the synthesis and radiolabeling of the NTP 15-5 with 99mTc, (2) preclinical scintigraphic imaging using laboratory animals, and (3) quantitative analysis of scintigraphic images.

Key words

Proteoglycans Scintigraphy 99mTc-NTP 15-5 radiotracer Quantitative imaging 

Notes

Acknowledgments

In our group, studies related to the in vivo scintigraphy of proteoglycans for the imaging of cartilage and its degenerative and tumoral pathologies are supported by the Regional Fund for Innovation (FRI 2) OSEO, the Contrat de Projet Etat Region (CPER), the Fondation pour la Recherche Médicale (FRM), the Ligue Contre Le Cancer, and the Institut National du Cancer.

Studies aiming at validating 99mTc-NTP 15-5 radiotracer as a candidate for clinical imaging of cartilage pathologies in nuclear medicine are conducted in close collaboration with Cyclopharma Laboratoires.

The authors would like to thank Prof. D. Heymann, Prof. F. Gouin, and Dr. F. Rédini from UMR S957 INSERM from Nantes University for their collaboration and expertise on chondrosarcoma.

References

  1. 1.
    Biswal, S., Resnick, D. L., Hoffman, J. M., and Gambhir, S. S. (2007) Molecular imaging: integration of molecular imaging into the musculoskeletal imaging practice. Radiology 244, 651–671.PubMedCrossRefGoogle Scholar
  2. 2.
    Vanderheyden, J. L. (2009) The use of imaging in preclinical drug development. Q J Nucl Med Mol Imaging 53, 374–381.PubMedGoogle Scholar
  3. 3.
    Weissleder, R. (2006) Molecular imaging in cancer. Science 312, 1168–1171.PubMedCrossRefGoogle Scholar
  4. 4.
    Meikle, S. R., Kench, P., Kassiou, M., and Banati, R. B. (2005) Small animal SPECT and its place in the matrix of molecular imaging technologies. Phys Med Biol. 50, R45–R61.PubMedCrossRefGoogle Scholar
  5. 5.
    Madelmont, J. C., Giraud, I., Nicolas, C., Maurizis, J. C., Rapp, M., Ollier, M., et al. (2001) Novel quaternary ammonium derivatives, method for preparing same and pharmaceutical use. Patent WO/2001/000621 PCT/FR2000/001731.Google Scholar
  6. 6.
    Maurizis, J. C., Rapp, M., Nicolas, C., Ollier, M., Verny, M., and Madelmont, J. C. (2000) Disposition in rats of N-pyridinium-propyl-cyclam, N-triethy-lammonium-propyl-cyclam, and N-[triethylammonium]-3-propyl-[15]ane-N5, potential cartilage imaging agents. Drug Metab Dispos. 28, 418–422.PubMedGoogle Scholar
  7. 7.
    Banerjee, S. R., Maresca, K. P., Francesconi, L., Valliant, J., Babich, J. W., and Zubieta, J. (2005) New directions in the coordination chemistry of 99mTc: a reflection on technetium core structures and a strategy for new chelate design. Nucl Med Biol. 32, 1–20.PubMedCrossRefGoogle Scholar
  8. 8.
    Ollier, M., Maurizis, J. C., Nicolas, C., Bonafous, J., De Latour, M., Veyre, A., and Madelmont, J. C. (2001) Joint scintigraphy in rabbits with 99mTc-N-[3-(triethylammonio)propyl]-15ane-N5,a new radiodiagnostic agent for articular cartilage imaging. J Nucl Med. 42, 141–145.PubMedGoogle Scholar
  9. 9.
    Miot-Noirault, E., Vidal, A., Pastoureau, P., Bonafous, J., Chomel, A., Sarry, L., et al. (2007) Early detection and monitoring of cartilage alteration in the experimental meniscectomized guinea pig model of osteoarthritis by 99mTc-NTP 15–5 scintigraphy. Eur J Nucl Med Mol Imaging 34, 1280–1290.PubMedCrossRefGoogle Scholar
  10. 10.
    Miot-Noirault, E., Vidal, A., Auzeloux, P., Madelmont, J. C., Maublant, J., and Moins, N. (2008) First In Vivo SPECT Imaging of Mouse Femorotibial Cartilage Using 99mTc-NTP 15–5. Mol Imaging 7, 263–271.PubMedGoogle Scholar
  11. 11.
    Miot-Noirault, E., Gouin, F., Vidal, A., Rapp, M., Maublant, J., Askienazy, S., et al. (2009) First preclinical imaging of primary cartilage neoplasm and its local recurrence using 99mTc-NTP 15–5 radiotracer. J Nucl Med. 50, 1541–1547.PubMedCrossRefGoogle Scholar
  12. 12.
    Lamoureux, F., Picarda, G., Garrigue-Antar, L., Baud’huin, M., Trichet, V., Vidal, A., et al. (2009) Glycosaminoglycans as potential regulators of osteoprotegerin therapeutic activity in osteosarcoma. Cancer Res. 69, 526–36.PubMedCrossRefGoogle Scholar
  13. 13.
    Sarda-Mantel, L. and Le Guludec, D. (2009) Molecular imaging of cartilage; invited perspectives. J Nucl Med. 50, 1391–1393.PubMedCrossRefGoogle Scholar
  14. 14.
    Wang, Q., Zheng, Y. P., Qin, L., Huang, Q. H., Lam, W. L., Leung, G., Guo, X., and Lu, H. B. (2008) Real-time ultrasonic assessment of progressive proteoglycan depletion in articular cartilage. Ultrasound Med Biol. 34, 1085–1092.PubMedCrossRefGoogle Scholar
  15. 15.
    Nieminen, M. T., Rieppo, J., Silvennoinen, J., Töyräs, J., Hakumäki, J. M., Hyttinen, M. M., et al. (2002) Spatial assessment of articular proteoglycans with Gd-DTPA-Enhanced T1 imaging. Magn Reson Med. 48, 640–648.PubMedCrossRefGoogle Scholar
  16. 16.
    Laurent, D., Wasvary, J., Rudin, M., O’Byrne, E., and Pellas, T. (2003) In vivo assessment of macromolecular content in articular cartilage of the goat knee. Magn Reson Med. 49, 1037–1046.PubMedCrossRefGoogle Scholar
  17. 17.
    Eckelman, W. C., Reba, R. C., and Kelloff, G. J. (2008) Targeted imaging: an important biomarker for understanding disease progression in the era of personalized medicine. Drug Discov Today 13, 748–759.PubMedCrossRefGoogle Scholar
  18. 18.
    Hardingham, T. E. and Fosang, A. J. (1992). Proteoglycans : many forms and many functions. FASEB J 6, 861–870.PubMedGoogle Scholar
  19. 19.
    Lamoureux, F., Baud’huin, M., Duplomb, L., Heymann, D., and Rédini, F. (2007) Proteoglycans : key partners in bone cell biology. Bioessays 29, 758–771.PubMedCrossRefGoogle Scholar
  20. 20.
    Schaefer, L., and Schaefer, R. M. (2010) Proteoglycans: from structural compounds to signaling molecules. Cell Tissue Res. 339, 237–246.PubMedCrossRefGoogle Scholar
  21. 21.
    Borges, L. F., Touat, Z., Leclercq, A., Zen, A. A., Jondeau, G., Franc, B., et al. (2009) Tissue diffusion and retention of metalloproteinases in ascending aortic aneurysms and dissections. Hum Pathol. 40, 306–313.PubMedCrossRefGoogle Scholar
  22. 22.
    Jeon, W. S., Kim, E., Ko, Y. H., Hwang, H., Lee, J. W., Kim, S.-Y., et al. (2004) Molecular Loop Lock: A Redox-Driven Molecular Machine Based on a Host-Stabilized Charge-Transfer Complex. Angew Chem. Int. Edit. 44, 87–91.CrossRefGoogle Scholar
  23. 23.
    Botero Cid, M. H., Holzgrabe, U., Kostenis, E., Mohr, K., and Traenkle, C. (1994) Search for the Pharmacophore of Bispyridinium-Type Allosteric Modulators of Muscarinic Receptors. J Med Chem. 37, 1439–1445.CrossRefGoogle Scholar
  24. 24.
    Loening, A. M. and Gambhir, S. S. (2003) AMIDE: a free software tool for multimodality medical image analysis. Mol Imaging 2, 131–137.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Elisabeth Miot-Noirault
    • 1
    • 2
    Email author
  • Aurélien Vidal
    • 1
    • 3
  • Philippe Auzeloux
    • 1
    • 2
  • Caroline Peyrode
    • 1
    • 2
  • Jean-Claude Madelmont
    • 1
    • 2
  • Jean-Michel Chezal
    • 1
    • 2
  1. 1.INSERM, UMR 990Clermont-FerrandFrance
  2. 2.Imagerie moléculaire et thérapie vectoriséeClermont Université, Université d’AuvergneClermont-FerrandFrance
  3. 3.Imagerie moléculaire et thérapie vectoriséeClermont Université, Université d’AuvergneClermont-FerrandFrance

Personalised recommendations