Advertisement

A new animal model for the imaging of melanoma: correlation of FDG PET with clinical outcome, macroscopic aspect and histological classification in Melanoblastoma-bearing Libechov Minipigs

  • Raphaël Boisgard
  • Silvia Vincent-NaulleauEmail author
  • Jean-Jacques Leplat
  • Stephan Bouet
  • Catherine Le Chalony
  • Yves Tricaud
  • Vratislav Horak
  • Claudine Geffrotin
  • Gérard Frelat
  • Bertrand Tavitian
Original Article

Abstract

The aim of this study was to evaluate the Melanoblastoma-bearing Libechov Minipigs (MeLiM) as an animal model of melanoma for in vivo imaging. Serial whole-body 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG PET) scans were conducted on five MeLiM. In order to explore different clinical stages of the tumoural lesions, each animal was scanned two to four times, at intervals of 30–155 days. PET images were analysed by a semiquantitative method based on the tumour to muscle metabolic ratio. Histology was performed on biopsies taken between or after the scans and the histological grading of the tumours was compared with the FDG uptake. The overall sensitivity of FDG PET for the detection of cutaneous melanoma was 75%; 62.5% of involved lymph nodes were positive. Sensitivity was better for tumours with vertical growth than for flat lesions. FDG PET did not detect tumours with epidermal involvement only, nor did it detect small metastatic foci. The metabolic ratio was correlated with the evolution of the melanoma. FDG PET is effective in the staging of cutaneous melanoma and the follow-up of tumoural extension and regression in Melanoblastoma-bearing Libechov Minipigs. The results obtained in this animal model correlate well with those described in human melanoma. Accordingly, this model may be useful in testing new tracers specific for melanoma and in helping to detect molecules expressed early during tumoural regression.

Keywords

Melanoma 2-Deoxy-2-[18F]fluoro-d-glucose MeLiM swine model regression 

Notes

Acknowledgments

The authors wish to thank Philippe Bacon and Jean-François Dossin for animal care, Vincent Brulon and Franck Mathieu for PET performance and Dr. Régine Trebossen for advice and discussion. R.B. and B.T. are supported by European contract QLG1-CT-2000-00562. Works in LREG and IAPG are supported by ARC grant 9450, EDF contract 8703, Grant Agency of the Czech Republic (no. 524/01/0162) and Integrated Actions Program (French Foreign Office France/Czech Republic, Barande contract no. 04710WJ).

References

  1. 1.
    Thomas L, Cochran AJ. Prise en charge du mélanome cutané. Cancer Radiother 1998; 2:732–746.Google Scholar
  2. 2.
    Masback A, Olsson H, Westerdahl J, Ingvar C, Jonsson N. Prognostic factors in invasive cutaneous malignant melanoma. a population-based study and review. Melanoma Res 2001; 11:435–445.Google Scholar
  3. 3.
    Krug B, Dietlein M, Groth W, Stutzer H, Psaras T, Gossmann A, Scheidhauer K, Schicha H, Lackner K. Fluor-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in malignant melanoma. Diagnostic comparison with conventional imaging methods. Acta Radiol 2000; 41:446–452.Google Scholar
  4. 4.
    Jadvar H, Johnson DL, Segall GM. The effect of fluorine-18 fluorodeoxyglucose positron emission tomography on the management of cutaneous malignant melanoma. Clin Nucl Med 2000; 25:48–51.Google Scholar
  5. 5.
    Stas M, Stroobants S, Dupont P, Gysen M, Hoe LV, Garmyn M, Mortelmans L, Wever ID. 18-FDG PET scan in the staging of recurrent melanoma: additional value and therapeutic impact. Melanoma Res 2002; 12:479–490.Google Scholar
  6. 6.
    Eigtved A, Andersson AP, Dahlstrom K, Rabol A, Jensen M, Holm S, Sorensen SS, Drzewiecki KT, Hojgaard L, Friberg L. Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma. Eur J Nucl Med 2000; 27:70–75.Google Scholar
  7. 7.
    Tyler DS, Onaitis M, Kherani A, Hata A, Nicholson E, Keogan M, Fisher S, Coleman E, Seigler HF. Positron emission tomography scanning in malignant melanoma. Cancer 2000; 89:1019–1025.Google Scholar
  8. 8.
    Acland KM, O'Doherty MJ, Russell-Jones R. The value of positron emission tomography scanning in the detection of subclinical metastatic melanoma. J Am Acad Dermatol 2000; 42:606–611.Google Scholar
  9. 9.
    Damian DL, Fulham MJ, Thompson E, Thompson JF. Positron emission tomography in the detection and management of metastatic melanoma. Melanoma Res 1996; 6:325–329.Google Scholar
  10. 10.
    Prichard RS, Hill AD, Skehan SJ, O'Higgins NJ. Positron emission tomography for staging and management of malignant melanoma. Br J Surg 2002; 89:389–396.Google Scholar
  11. 11.
    Herlyn M. Emerging concepts and technologies in melanoma research. Melanoma Res 2002; 12:3–8.Google Scholar
  12. 12.
    Zhang Z, Monteiro-Rivière A. Comparison of integrins in human skin, pig skin, and perfused skin: an in vitro skin toxicology model. J Appl Toxicol 1997; 17:247–253.Google Scholar
  13. 13.
    Millikan LE, Boylon JL, Hook RR, Manning PJ. Melanoma in Sinclair swine: a new animal model. J Invest Dermatol 1974; 62:20–30.Google Scholar
  14. 14.
    Müller S, Wanke R, Distl O. Inheritance of melanocytic lesions and their association with the white colour phenotype in miniature swine. J Anim Breed Genet 2001; 118:275–283.Google Scholar
  15. 15.
    Horak V, Fortyn K, Hruban V, Klaudy J. Hereditary melanoblastoma in miniature pigs and its successful therapy by devitalization technique. Cell Mol Biol 1999; 45:1119–1129.Google Scholar
  16. 16.
    Greene JF, Townsend JS, Amoss MS. Histopathology of regression in Sinclair swine model of melanoma. Lab Invest 1994; 71:17–24.Google Scholar
  17. 17.
    McGovern VJ, Cochran AJ, Van der Esch EP, Little JH, MacLennan R. The classification of malignant melanoma, its histological reporting and registration: a revision of the 1972 Sydney classification. Pathology 1986; 18:12–21.Google Scholar
  18. 18.
    Clark WH Jr, From L, Bernardino EA, Mihm MC. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 1969; 29:705–727.Google Scholar
  19. 19.
    Ak L, Stokkel MPM, Bergman W, Pauwels EKJ. Cutaneous malignant melanoma: clinical aspects, imaging modalities and treatment. Eur J Nucl Med 2000; 27:447–458.Google Scholar
  20. 20.
    Meyer W, Schwarz R, Neurand K. The skin of domestic mammals as a model for the human skin, with special reference to the domestic pig. Curr Probl Dermatol 1978; 7:39–52.Google Scholar
  21. 21.
    Wagner JD, Schauwecker DS, Davidson D, Wenck S, Jung SH, Hutchins G. FDG-PET sensitivity for melanoma lymph node metastases is dependent on tumour volume. J Surg Oncol 2001; 77:237–242.Google Scholar
  22. 22.
    Acland KM, Healy C, Calonje E, O'Doherty M, Nunan T, Page C, Higgins E, Russell-Jones R. Comparison of positron emission tomography scanning and sentinel node biopsy in the detection of micrometastases of primary cutaneous malignant melanoma. J Clin Oncol 2001; 19:2674–2678.Google Scholar
  23. 23.
    Goerres GW, Stoeckli SJ, von Schulthess GK, Steinert HC. FDG PET for mucosal malignant melanoma of the head and neck. Laryngoscope 2002; 112:381–385.Google Scholar
  24. 24.
    Crippa F, Leutner M, Belli F, Gallino F, Greco M, Pilotti S, Cascinelli N, Bombardieri E. Which kinds of lymph node metastases can FDG PET detect? A clinical study in melanoma. J Nucl Med 2000; 41:1491–1494.Google Scholar
  25. 25.
    Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, Mozley PD, Rossman MD, Albelda SM, Alavi A. Dual time point18F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med 2001; 42:1412–1417.Google Scholar
  26. 26.
    Das Gupta TK, Ronan SG, Beattie CW, Shilkaitis A, Amoss MS. Comparative histology of porcine and human cutaneous melanoma. Pediatr Dermatol 1989; 6:289–299.Google Scholar
  27. 27.
    Barnetson RSC, Halliday GM. Regression in skin tumours: a common phenomenon. Australas J Dermatol 1997; 38:S63–S65.Google Scholar
  28. 28.
    Menzies SW, McCarthy WH. Complete regression of primary cutaneous malignant melanoma. Arch Surg 1997; 132:553–556.Google Scholar
  29. 29.
    Oxenhandler RW, Adelstein EH, Haigh JP, Hook RR Jr, Clark WH Jr. Malignant melanoma in the Sinclair miniature swine. An autopsy study of 60 cases. Am J Pathol 1979; 96:707–720.Google Scholar
  30. 30.
    Peng N, Yen S, Liu W, Tsay D, Liu R. Evaluation of the effect of radiation therapy to nasopharyngeal carcinoma by positron emission tomography with 2-[F18]fluoro-2-deoxy-d-glucose. Clin Positron Imaging 2000; 3:51–56.Google Scholar
  31. 31.
    Heelan BT, Osman S, Blyth A, Schnorr L, Jones T, George AJ. Use of 2-[18F]fluoro-2-deoxyglucose as a potential agent in the prediction of graft rejection by positron emission tomography. Transplantation 1998; 66:1101–1103.Google Scholar
  32. 32.
    Dalsaso TA, Lowe VJ, Dunphy FR, Martin DS, Boyd JH, Stack BC. FDG-PET and CT in evaluation of chemotherapy in advanced head and neck cancer. Clin Positron Imaging 2000; 3:1–5.Google Scholar
  33. 33.
    Nair N, Ali A, Green AA, Lamonica G, Alibazoglu H, Alibazoglu B, Hollinger EF, Ahmed K. Response of osteosarcoma to chemotherapy. Evaluation with F-18 FDG-PET scans. Clin Positron Imaging 2000; 3:79–83.Google Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Raphaël Boisgard
    • 1
  • Silvia Vincent-Naulleau
    • 2
    Email author
  • Jean-Jacques Leplat
    • 2
  • Stephan Bouet
    • 2
  • Catherine Le Chalony
    • 2
  • Yves Tricaud
    • 2
  • Vratislav Horak
    • 3
  • Claudine Geffrotin
    • 2
  • Gérard Frelat
    • 2
  • Bertrand Tavitian
    • 1
  1. 1.Laboratoire d'imagerie de l'expression des gènes, CEA, Service hospitalier Frédéric JoliotINSERM 0103OrsayFrance
  2. 2.Laboratoire de Radiobiologie et d'Etude du Génome Joint CEA INRA Research UnitJouy-en-JosasFrance
  3. 3.Institute of Animal Physiology and GeneticsAcademy of Sciences of the Czech RepublicLibechovCzech Republic

Personalised recommendations