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Cytotoxic and antitumor effects of the norepinephrine analogue meta-iodo-benzylguanidine (MIBG)

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  • Norepinephrine Analogue, MIBG
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Summary

Meta-iodo-benzylguanidine (MIBG) is an analogue of the neurotransmitter norepinephrine. In its radio-iodinated form, MIBG is clinically used as a tumor-targeted radiopharmaceutical in the diagnosis and treatment of adrenergic tumors. The potential cytotoxicity of the unlabeled drug was tested. MIBG appeared cytotoxic in a large panel of histogenetically different cell lines without preference against tumor cells of neural origin. The cytotoxicity of MIBG was higher than of the related mono-amine precursor, meta-iodo-benzylamine (MIBA). Drugs that block adrenergic receptors and inhibitors of tyrosinase or tyrosine hydroxylase had no effect on the cytostatic properties of MIBG. However, its activity was potentiated by the pharmacological inhibition of catecholamine degradation and by inhibitors of intracellular storage. MIBG had antitumor effects on L1210 leukemia and N1E115 neuroblastoma, grown as subcutaneous tumors in animals treated with MIBG in non-toxic schedules. The observations suggest that MIBG is cytotoxic in its native form and may contribute by this property to the clinical responses obtained with the radiolabeled drug at high concentrations.

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References

  1. Berger NA (1986) Cancer chemotherapy: new strategies for success. J Clin Invest 78: 1131

    Google Scholar 

  2. Bruchelt G, Buck J, Girgert R, Treuner J, Niethammer D (1985) The role of reactive oxygen compounds derived from 6-hydroxydopamine for bone marrow purging from neuroblastoma cells. Biochem Biophys Res Commun 130: 168

    Google Scholar 

  3. Geran RI, Greenberg NH, MacDonald MM, Schumacher AM, Abbot BJ (1972) Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemother Rep 3: 1

    Google Scholar 

  4. Hoefnagel CA, Voûte PA, De Kraker J, Marcuse HR (1985) Total-body scintigraphy with 131I-meta-iodobenzylguanidine for detection of neuroblastoma. Diagn Imag Clin Med 54: 21

    Google Scholar 

  5. Hoefnagel CA, Voûte PA, De Kraker J, Marcuse HR (1987) Radionuclide diagnosis and therapy of neural crest tumors using I-131-meta-iodobenzylguanidine. J Nucl Med 28: 308

    Google Scholar 

  6. Mekalanos JJ, Collier RJ, Ranig WR (1979) Enzymatic activity of cholera toxin. I. New method of assay and the mechanism of ADP-ribosyl transfer. J Biol Chem 254: 5849

    Google Scholar 

  7. Moore KE, Dominic JA (1971) Tyrosine hydroxylase inhibitors. Fed Proc 30: 859

    Google Scholar 

  8. Morrison ME, Yagi MJ, Cohen G (1985) In vitro studies of 2,4-dihydroxyphenylalanine, a prodrug targeted against malignant melanoma cells. Proc Natl Acad Sci USA 82: 2960

    Google Scholar 

  9. Sisson JC, Marc SF, Valk TW, Gross MD, Swanson DP, Wieland DM, Tobes MC, Beierwaltes WH, Thompson NW (1981) Scintigraphic localization of pheochromocytoma. New Engl J Med 305: 12

    Google Scholar 

  10. Sisson JC, Shapiro B, Beierwaltes WH, Glowniak JV, Nakajo M, Manger TJ, Carey JE, Swanson DP, Copp JE, Satterlee WG, Wieland DM (1984) Radiopharmaceutical treatment of malignant pheochromocytoma. J Nucl Med 24: 197

    Google Scholar 

  11. Spencer R, Leutzinger E, Spitznagle L, Hosain F, Jain N, Kolstad K (1986) Problem with mouse neuroblastoma (C1300) as a model for iodine-131 MIBG uptake. J Nucl Med 27: 726

    Google Scholar 

  12. Tobes MC, Sandford J, Wieland DM, Sisson JC (1985) Effect of uptake-one inhibitors on the uptake of norepinephrine and metaiodobenzylguanidine. J Nucl Med 26: 897

    CAS  PubMed  Google Scholar 

  13. Ueda K, Hayaishi O (1985) ADP-ribosylation. Ann Rev Biochem 54: 73

    Google Scholar 

  14. Weiner N, Taylor P (1985) Drugs acting at synaptic and neuroeffector junctional sites. In: Giman A, Goodman LS, Rall TW, Murad F (eds) Goodman and Gilman's: the pharmacological basis of therapeutics. Macmillan, New York, pp 66–236

    Google Scholar 

  15. Wick MM, Byers L, Frei E (1977) l-dopa selective toxicity for melanoma cell in vitro. Science 197: 468

    Google Scholar 

  16. Wieland DM, Wu JI, Brown LW, Manger TJ, Swanson DP, Beierwaltes WH (1980) Radiolabeled adrenergic neuronblocking agents: adrenomedullary imaging with (131I) iodobenzylguanidine. J Nucl Med 21: 349

    Google Scholar 

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Authors and Affiliations

  1. Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    Lou A. Smets, Bram Bout & Josieneke Wisse

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  1. Lou A. Smets
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  2. Bram Bout
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  3. Josieneke Wisse
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Smets, L.A., Bout, B. & Wisse, J. Cytotoxic and antitumor effects of the norepinephrine analogue meta-iodo-benzylguanidine (MIBG). Cancer Chemother. Pharmacol. 21, 9–13 (1988). https://doi.org/10.1007/BF00262730

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  • DOI: https://doi.org/10.1007/BF00262730

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