Skip to main content
SpringerLink
Log in

Autoradiographic distribution of [14C]-labelled pimonidazole in rhabdomyosarcoma-bearing rats and pigmented mice

  • Original Articles
  • Autoradiography, Hypoxic Cell, Rhabdomyosarcoma
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

The hypoxic cell radiosensitizer [2-14C] pimonidazole (2-nitro-α-(piperidinomethyl)-l-imidazole ethanol) was injected i.p. into pigmented mice and rats bearing transplanted rhabdomyosarcoma. The injected dose level was 200 mg/kg, and the delivered activity was 96 μCi/kg. Whole-body autoradiography was carried out on all animals. We noted an extensive whole-body distribution of radioactivity. At short intervals, the autoradiograms were characterized by an accumulation of radioactivity in the metabolic and exretory organs (liver, kidney, urinary tract, and intestinal content) as well as in lymphomyeloid tissues (thyroid gland, suprarenal gland, and hypophysis) and salivary glands. In pigmented mice, the uveal and biliary tracts were the highest labelled. The liver and particularly the renal medulla were identified as sites of retention of radioactivity. In the tumor the radioactivity was detected only in peripheral regions, with higher uptake in viable zones than in necrotic islets.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

MISO:

misonidazole

[14C] ou [14C] Ro, [14C]:

Ro 03-8799 plus Ro 03-8799-derived [14C]-labelled metabolites

References

  1. Akel G, Benard P, Canal P, Soula G (1986) Distribution and tumor penetration properties of radiosensitizer [2-14C] misonidazole (Ro 07-0582) in mice and rats as studied by wholebody autoradiography. Cancer Chemother Pharmacol 17: 121

    Google Scholar 

  2. Allen JG, Dische S, Lenox-Smith I, Malcolm SL, Saunders MI (1984) The pharmacokinetics of a new radiosensitizer, Ro 03-8799, in humans. Eur J Clin Pharmacol 27: 483

    Google Scholar 

  3. Blasberg R, Horowitz M, Strong J, Molmar P, Patlak C, Owens E, Fenstermacher J (1985) Regional measurements of [14C] misonidazole distribution and blood flow in subcutaneous RT-9 experimental tumors. Cancer Res 45: 1692

    Google Scholar 

  4. Dische S, Saunders MI, Lee ME, Admas GE, Flockhart IR (1977) Clinical testing of the radiosensitizer Ro 07-0582: experience with multiple doses. Br J Cancer 35: 567

    Google Scholar 

  5. Dische S, Saunders MI, Dunphy EP, Bennett MH, Desrochers C, Stratford MRL, Minchinton AI, Orchard RA (1986a) Concentrations achieved in human tumors after administration of misonidazole, SR-2508 and Ro 03-8799. Int J Radiat Oncol Biol Phys 12: 1109

    Google Scholar 

  6. Dische S, Saunders MI, Bennett MH, Wardman P (1986b) A comparison of the tumour concentrations obtainable with misonidazole and Ro 03-8799. Br J Radiol 59: 911

    Google Scholar 

  7. Durand S, Benard P, Braun JP (1980) Ethionine and methionine distribution and toxicity in the rat kidney. Toxicol Lett 5: 257

    Google Scholar 

  8. Gessner T, Trudnowski R, Rico R, Rempel J (1976) Passage of intravenously administered pethidine into gastric juice in man. J Pharm Pharmacol 28: 79

    Google Scholar 

  9. Lindquist NG (1973) Accumulation of drugs on melanin. Acta Radiol 325 (Suppl): 1

    Google Scholar 

  10. Malcolm SL, Lee A, Groves JK (1983) HPLC analysis of Ro 03-8799 in biological samples. J Chromatogr 273: 327

    Google Scholar 

  11. Newman HFV, Bleehen NM, Workman P (1986) A phase I study of the combination of two hypoxic cell radiosensitizers, Ro 03-8799 and SR-2508: toxicity and pharmacokinetics. Int J Radiat Oncol Biol Phys 12: 1113

    Google Scholar 

  12. Rich TA, Dische S, Saunders MI, Stratford MRL, Minchinton A (1981) A serial study of the concentration of misonidazole in human tumors correlated with histologic structure. Int. J Radiat Oncol Biol Phys 7: 197

    Google Scholar 

  13. Roberts JT, Bleehen NM, Walton MI, Workman P (1986) A clinical phase I toxicity study of Ro 03-8799: plasma, urine, tumour and normal brain pharmacokinetics. Br J Radiol 59: 107

    Google Scholar 

  14. Saunders MI, Dische S, Fermont D, Bishop A, Lenox-Smith I, Allen JG, Malcolm SL (1982) The radiosensitizer Ro 03-8799 and the concentrations which may be achieved in human tumours: a preliminary study. Br J Cancer 46: 706

    Google Scholar 

  15. Saunders MI, Anderson PJ, Bennett MH, Dische S, Minchinton A, Stratford MRL, Tothill M (1984) The clinical testing of Ro 03-8799 pharmacokinetics, toxicology, tissue and tumor concentrations. Int J Radiat Oncol Biol Phys 10: 1759

    Google Scholar 

  16. Smithen CE, Clarke ED, Dale JA, Jacobs RS, Wardman P, Watts ME, Woodcock M (1980) Novel (nitro-1-imidazolyl) alkanolamines as potential radiosensitizers with improved therapeutic properties. In: Brady LH (ed) Radiation sensitizers: their use in the clinical management of cancer. Masson, New York pp 22

    Google Scholar 

  17. Sweeney FL, Pot-Derpum J, Poupon MF, Chouroulinkov I (1982) Heterogeneity of the growth and metastatic behavior of cloned cell lines derived from a primary rhabdomyosarcoma. Cancer Res 42: 3776

    Google Scholar 

  18. Ullberg S (1977) The technique of whole-body autoradiographic study. Sci Tools 2

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Biochimie Appliquée de la Faculté des Sciences Pharmaceutiques, 35 chemin des Maraîchers, F-31062, Toulouse Cedex, France

    François Laurent & Georges Soula

  2. Laboratoire des Radioéléments et d'études métaboliques, Ecole Nationale Vétérinaire-I.N.R.A., 23 chemin des Capelles, F-31076, Toulouse, Cedex, France

    Patrick Benard

  3. Groupe de Recherches Carcinologiques, Centre Claudius Regaud, 20, 24 rue du Pont Saint-Pierre, F-31052, Toulouse Cedex, France

    Pierre Canal & Georges Soula

Authors
  1. François Laurent
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick Benard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pierre Canal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Georges Soula
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Laurent, F., Benard, P., Canal, P. et al. Autoradiographic distribution of [14C]-labelled pimonidazole in rhabdomyosarcoma-bearing rats and pigmented mice. Cancer Chemother. Pharmacol. 22, 308–315 (1988). https://doi.org/10.1007/BF00254237

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00254237

Keywords

Search

Navigation