Skip to main content
Log in

Early detection and monitoring of cartilage alteration in the experimental meniscectomised guinea pig model of osteoarthritis by 99mTc-NTP 15-5 scintigraphy

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

This study in the meniscectomised guinea pig aimed to demonstrate that the radiotracer 99mTc-NTP 15-5 would have pathophysiological validity for in vivo osteoarthritis imaging.

Methods

The specificity of 99mTc-NTP 15-5 for cartilage was determined in healthy animals (n = 13), by tissue radioactivity counting, joint autoradiography and scintigraphy. 99mTc-NTP 15-5 scintigraphy was performed at 20, 50, 80, 115, 130, 150 and 180 days after medial meniscectomy (n = 10 MNX) or sham operation (n = 5), and scintigraphic ratios (operated/contralateral) were calculated for femoral (F) and tibial (T) areas. F and T ratios were compared with those of 99mTc-MDP bone scintigraphy. At the study end-point, autoradiographic analysis of joint 99mTc-NTP 15-5 distribution and macroscopic scoring of cartilage integrity were performed.

Results

The high and specific accumulation of 99mTc-NTP 15-5 in normal cartilage (about 5.5 ± 1.7 % of injected dose/g of tissue), which permitted joint imaging with high contrast, was affected by osteoarthritis. In the MNX group, 99mTc-NTP 15-5 accumulation in cartilage within the operated joint, relative to the contralateral joint, was observed to change in the same animals as pathology progressed. Although F and T ratios were significantly higher in MNX (F = 1.7 ± 0.2; T = 1.6 ± 0.1) than in shams (F = 1.0 ± 0.1; T = 1.0 ± 0.1) at day 50, they were significantly lower in MNX (F = 0.6 ± 0.1; T = 0.7 ± 0.1) than in shams (F = 1.0 ± 0.1; T = 0.9 ± 0.1) at day 180. No change in 99mTc-MDP uptake was observed over 6 months. Macroscopic analysis confirmed features of osteoarthritis only in MNX knees.

Conclusion

These results in MNX guinea pigs provide additional support for the use of 99mTc-NTP 15-5 for in vivo imaging of osteoarthritis.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Reginster JY. The prevalence and burden of osteoarthritis. Rheumatology 2002;41 Suppl 1:3–6.

    Article  PubMed  Google Scholar 

  2. Martel-Pelletier J. Pathophysiology of osteoarthritis. Osteoarthr Cartil 1999;7:371–3.

    Article  CAS  PubMed  Google Scholar 

  3. Martel-Pelletier J, di Battista J, Lajeunesse D. Biochemical factors in joint articular degradation osteoarthritis. In: Reginster JY, Pelletier JP, Martel-Pelletier J, Henrotin Y, editors. Osteoarthritis: clinical and experimental aspects. Berlin: Springer-Verlag; 1999; p. 156–87.

    Google Scholar 

  4. Blackburn WD Jr, Chivers S, Bernreuter W. Cartilage imaging in osteoarthritis. Semin Arthritis Rheum 1996;25:273–81.

    Article  PubMed  Google Scholar 

  5. Ravaud P, Giraudeau B, Auleley GR, Drape JL, Rousselin B, Paolozzi L, et al. Variability in knee radiographing: implication for definition of radiological progression in medical knee osteoarthritis. Ann Rheum Dis 1998;57:624–9.

    Article  CAS  PubMed  Google Scholar 

  6. Abadie E, Ethgen D, Avouac B, Bouvenot G, Branco J, Bruyere O, et al. Recommendations for the use of new methods to assess the efficacy of disease-modifying drugs in the treatment of osteoarthritis. Osteoarthr Cartil 2004;12:263–8.

    Article  PubMed  Google Scholar 

  7. Pelletier JP, Martel-Pelletier J. Therapeutic targets in osteoarthritis: from today to tomorrow with new imaging technologies. Ann Rheum Dis 2003;62 Suppl 2:ii79–82.

    PubMed  Google Scholar 

  8. Dougados M. Monitoring osteoarthritis progression and therapy. Osteoarthr Cartil 2004;12 Suppl A:S55–60.

    Article  PubMed  Google Scholar 

  9. Asghar K, Roth LJ. Distribution of hexamethonium and other quaternary ammonium compounds in cartilage. J Pharmacol Exp Ther 1971;176:83–92.

    CAS  PubMed  Google Scholar 

  10. Larsson B, Nilsson M, Tjalve H. The binding of inorganic and organic cations and H+ to cartilage in vitro. Biochem Pharmacol 1981;30:2963–70.

    Article  CAS  PubMed  Google Scholar 

  11. Garrigue H, Maurizis JC, Madelmont JC, Nicolas C, Meyniel JM, Louvel A, et al. Disposition and metabolism of acetylcholinesterase reactivators 2PAM-I, TMB4 and R665 in rats submitted to organophosphate poisoning. Xenobiotica 1991;21:583–95.

    Article  CAS  PubMed  Google Scholar 

  12. Maurizis JC, Ollier M, Nicolas C, Madelmont JC, Garrigue H, Veyre A. In vitro binding of oxime acetylcholinesterase reactivators to proteoglycans synthesized by cultured chondrocytes and fibroblasts. Biochem Pharmacol 1992;44:1927–33.

    Article  CAS  PubMed  Google Scholar 

  13. Madelmont JC, Giraud I, Nicolas C, Maurizis JC, Rapp M, Ollier M, et al. French Patent 99,08020; 1999; June 23, 29 pp.

  14. Nicolas C, Verny M, Giraud I, Ollier M, Rapp M, Maurizis JC, et al. New quaternary ammonium oxicam derivatives targeted toward cartilage: synthesis, pharmacokinetic studies and anti-inflammatory potency. J Med Chem 1999;42:5235–40.

    Article  CAS  PubMed  Google Scholar 

  15. Giraud I, Rapp M, Maurizis JC, Madelmont JC. Application to a cartilage targeting strategy: synthesis and in vivo biodistribution of 14C-labeled quaternary ammonium-glucosamine conjugates. Bioconjug Chem 2000;11:212–8.

    Article  CAS  PubMed  Google Scholar 

  16. Nicolas C, Borel M, Maurizis JC, Gallais N, Rapp M, Ollier M, et al. Synthesis of N-quaternary ammonium [3H] and [99mTc] polyazamacrocycles, potential radiotracers for cartilage imaging. J Label Compd Radiopharm 2000;43:585–94.

    Article  CAS  Google Scholar 

  17. Maurizis JC, Rapp M, Nicolas C, Ollier M, Verny M, Madelmont JC. Disposition in rats of N-pyridinium-propyl-cyclam, N-triethylammonium-propyl-cyclam, and N-[triethylammonium]-3-propyl-[15]ane-N5, potential cartilage imaging agents. Drug Metab Dispos 2000;28:418–22.

    CAS  PubMed  Google Scholar 

  18. Ollier M, Maurizis JC, Nicolas C, Bonafous J, de Latour M, Veyre A, et al. Joint scintigraphy in rabbits with 99mTc-N-[3-(triethylammonio)propyl]-15ane-N5, a new radiodiagnostic agent for articular cartilage imaging. J Nucl Med 2001;42:141–5.

    CAS  PubMed  Google Scholar 

  19. Pritzker KH. Animal models for osteoarthritis: processes, problems and prospects. Ann Rheum Dis 1994;53:406–20.

    Article  CAS  PubMed  Google Scholar 

  20. Jouzeau JY, Gillet P, Netter P. Interest of animal models in the preclinical screening of anti-osteoarthritic drugs. Jt Bone Spine 2000;67:565–9.

    Article  CAS  Google Scholar 

  21. Smith M, Gosh P. Experimental models of osteoarthritis. In: Moskowitz RW, Howell DS, Altman RD, Buckwalter JA, Goldberg VM, editors. Osteoarthritis. Diagnosis and medical/surgical management. Philadelphia: WB Saunders; 2001; p. 171–99.

    Google Scholar 

  22. Bendele AM. Progressive chronic osteoarthritis changes in femorotibial joints of partial medial meniscectomized guinea pigs. Vet Pathol 1987;24:444–8.

    CAS  PubMed  Google Scholar 

  23. Bendele A, MC Comb J, Gould TY, McAbee T, Sennello G, Chlipala E, et al. Animal models of osteoarthritis: relevance to human disease. Toxicol Pathol 1999;27:134–42.

    CAS  PubMed  Google Scholar 

  24. Messner K, Fahlgren A, Ross I, Andersson B. Simultaneous changes in bone mineral density and articular cartilage in a rabbit meniscectomy model of knee osteoarthritis. Osteoarthr Cartil 2000;8:197–206.

    Article  CAS  PubMed  Google Scholar 

  25. Pastoureau P, Leduc M, Chomel A, De Ceuninck F. Quantitative assessment of articular cartilage and subchondral bone histology in the meniscectomized guinea pig model of osteoarthritis. Osteoarthr Cartil 2003;11:412–23.

    Article  CAS  PubMed  Google Scholar 

  26. Calvo E, Palacios I, Delgado E, Sanchez-pernaute O, Largo R, Egido J, et al. Histopathological correlation of cartilage swelling detected by magnetic resonance imaging in early experimental osteoarthritis. Osteoarthr Cartil 2004;12:878–86.

    Article  CAS  PubMed  Google Scholar 

  27. Havdrup T, Telhag H. Papain-induced changes in the knee joints of adult rabbits. Acta Orthop Scand 1977;48:143–9.

    Article  CAS  PubMed  Google Scholar 

  28. Adams ME, Matyas JR, Huang D, Dourado GS. Expression of proteoglycans and collagen in the hypertrophic phase of experimental osteoarthritis. J Rheumatol, Suppl 1995;43:94–7.

    CAS  Google Scholar 

  29. Venn G, Billingham ME, Hardingham TE. Increased proteoglycan synthesis in cartilage in experimental canine osteoarthritis does not reflect a permanent change in chondrocyte phenotype. Arthritis Rheum 1995;38:525–32.

    Article  CAS  PubMed  Google Scholar 

  30. Sandell LJ, Aigner T. Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res 2001;3:107–13.

    Article  CAS  PubMed  Google Scholar 

  31. Wei L, Svensson O, Hjerpe A. Proteoglycan turnover during development of spontaneous osteoarthrosis in guinea pigs. Osteoarthr Cartil 1998;6:410–6.

    Article  CAS  PubMed  Google Scholar 

  32. Brandt KD. Compensation and decompensation of articular cartilage in osteoarthritis. Agents Actions 1993;40:232–4.

    Article  CAS  PubMed  Google Scholar 

  33. Aigner T, Dudhia J. Phenotypic modulation of chondrocytes as a potential therapeutic target in osteoarthritis: a hypothesis. Ann Rheum Dis 1997;56:287–91.

    CAS  PubMed  Google Scholar 

  34. Mazzuca SA, Brandt KD, Schauwecker DS, Buckwalter KA, Katz BP, Meyer JM, et al. Bone scintigraphy is not a better predictor of progression of knee osteoarthritis than Kellgren and Lawrence grade. J Rheumatol 2004;31:329–32.

    PubMed  Google Scholar 

  35. Brandt KD, Schauwecker DS, Dansereau S, Meyer J, O’Connor B, Myers SL. Bone scintigraphy in the canine cruciate deficiency model of osteoarthritis. Comparison of the unstable and contralateral knee. J Rheumatol 1997;24:140–5.

    CAS  PubMed  Google Scholar 

  36. Dieppe P, Cushnaghan J, Young P, Kirwan J. Prediction of the progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy. Ann Rheum Dis 1993;52:557–63.

    CAS  PubMed  Google Scholar 

  37. Uno K, Suguro T, Nohira K, Moriya H, Saegusa K, Anzai Y, et al. Comparison of indium-111-labeled leukocyte scintigraphy and technetium-99m joint scintigraphy in rheumatoid arthritis and osteoarthritis. Ann Nucl Med 1992;6:247–51.

    Article  CAS  PubMed  Google Scholar 

  38. Roivainen A, Parkkola R, Yli-Kerttula T, Lehikoinen P, Viljanen T, Mottonen T, et al. Use of positron emission tomography with methyl-11C-choline and 2-18F-fluoro-2-deoxy-D-glucose in comparison with magnetic resonance imaging for the assessment of inflammatory proliferation of synovium. Arthritis Rheum 2003;48:3077–84.

    Article  CAS  PubMed  Google Scholar 

  39. Korn N, Huang CC, Seevers RH, Rothwell C, Counsell RE. Bisquaternary ammonium compounds as potential tumor imaging agents. Int J Nucl Med Biol 1979;6:153–61.

    Article  CAS  PubMed  Google Scholar 

  40. Yu SW, Shaw SM, Van Sickle DC. Radionuclide studies of articular cartilage in the early diagnosis of arthritis in the rabbit. Ann Acad Med Singap 1999;28:44–8.

    CAS  PubMed  Google Scholar 

  41. Meyer P, Burkhardt H, Palombo-Kinne E, Grunder W, Brauer R, Stiller KJ, et al. 123I-antileukoproteinase scintigraphy reveals microscopic cartilage alterations in the contralateral knee joints of rats with monoarticular antigen-induced arthritis. Arthritis Rheum 2000;43:298–310.

    Article  CAS  PubMed  Google Scholar 

  42. Kairemo KJA, Lappalainen AK, Kaapa E, Laitinen OM, Hyytinen T, Karonen SL, et al. In vivo detection of intervertebral disk injury using a radiolabeled monoclonal antibody against keratan sulfate. J Nucl Med 2001;42:476–82.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elisabeth Miot-Noirault.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miot-Noirault, E., Vidal, A., Pastoureau, P. et al. Early detection and monitoring of cartilage alteration in the experimental meniscectomised guinea pig model of osteoarthritis by 99mTc-NTP 15-5 scintigraphy. Eur J Nucl Med Mol Imaging 34, 1280–1290 (2007). https://doi.org/10.1007/s00259-006-0320-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-006-0320-2

Keywords

Navigation