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Increase in ω3 (Peripheral-Type Benzodiazepine) binding site densities in different types of human brain tumours

A quantitative autoradiography study

  • Neuropathological Articles
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Summary

The density of ω3 (peripheral type benzodiazepine) binding sites, a marker of reactive and tumoural cells, has been measured in different types of human brain tumours; ω3 sites were quantified autoradiographically in sections from biopsy or autopsy specimens labelled with the specific radioligand3H-PK 11195. Compared to normal brain parenchyma, up to 12-fold increase in ω3 site densities were found in appparently viable areas of high grade astrocytoma and glioblastoma specimens, whereas more limited increases (2 to 3-fold) in this marker were observed in areas of necrosis. Low grade gliomas (astrocytomas) and meningiomas exhibited only moderate increases (2 to 3-fold) in this autoradiographic marker. Metastases of lung or kidney origin were characterized by greatly elevated (up to 20-fold) ω3 site densities as compared to normal brain parenchyma. In every case, there was a good spatial correspondence between the histopathological limits of the tumour and the anatomical location of the increase in ω3 site densities. These results suggest that ω3 site densities in human brain tumours reflect their proliferative activity and point to a possible future usefulness of positron or gamma-ray emitting ω3 site ligands for the clinical investigation and detection of human brain proliferative diseases.

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References

  1. Ahlo H, Helen P, Harjuntausta T, Hervonen A, Krueger A (1990) Localization of peripheral-type benzodiazepine receptor and diazepam binding inhibitor-like immunoreactivity in human brain and cerebral tumors. Neurosci Abstract 16: 335

    Google Scholar 

  2. Benavides J, Fage D, Carter C, Scatton B (1987) Peripheral type benzodiazepine binding sites are a sensitive indirect index of neuronal damage. Brain Res 421: 167–172

    Google Scholar 

  3. Benavides J, Cornu P, Dennis T, Dubois A, Hauw JJ, MacKenzie ET, Sazdovitch V, Scatton B (1988) Imaging of humain brain lesions with an ω3 site radioligand. Ann Neurol 24: 708–712

    Google Scholar 

  4. Benavides J, Cornu P, Dubois A, Gotti B, MacKenzie ET, Scatton B (1989) ω3 binding sites as a tool for the detection and quantification of brain lesions: application to the evaluation of neuroprotective agents. In: Krieglstein J (ed) Pharmacology of cerebral ischaemia 1988. CRC Press, Boca Raton, pp 187–196

    Google Scholar 

  5. Benavides J, Dubois A, Dennis T, Hamel E, Scatton B (1989) ω3 (peripheral type benzodiazepine binding) site distribution in the rat immune system: an autoradiographic study with the photoaffinity ligand [3H-PK 14105]. J Pharmacol Exp Ther 249: 333–339

    Google Scholar 

  6. Benavides J, Capdeville C, Dauphin F, Dubois A, Duverger D, Fage D, Gotti B, MacKenzie ET, Scatton B (1990) The quantification of brain lesions with an ω3 site ligand: a critical analysis of animal models of cerebral ischaemia and neurodegeneration. Brain Res 522: 275–289

    Google Scholar 

  7. Benavides J, Dubois A, Gotti B, Bourdiol F, Scatton B (1990) Cellular distribution of ω3 (peripheral type benzodiazepine) binding sites in the normal and ischaemic rat brain: an autoradiographic study with the photoaffinity ligand3 H-PK 14105. Neurosci Lett 114: 32–38

    Google Scholar 

  8. Black KL, Ikezaki K, Santori E, Becker D, Vinters HV (1990) Specific high-affinity binding of peripheral benzodiazepine receptor ligands to brain tumors in rat and man. Cancer 65: 93–97

    Google Scholar 

  9. Cornu Ph, Benavides J, Hauw JJ, Pappata S, Samson Y, Scatton B, Philippon J (1991) ω3 binding sites as a tool for the in vivo detection of human malignant brain glioma. European Neurosurgery Meeting, Moscou, June 1991

  10. Doble A, Malgouris C, Daniel M, Daniel N, Imbault F, Basbaum A, Uzan A, Guérémy C, Le Fur G (1987) Labelling of peripheral-type benzodiazepine binding sites in humain brain with [3H] PK 11195: anatomical and subcellular distribution. Brain Res Bull 18: 49–61

    Google Scholar 

  11. Broaddus WC, Bennett JP (1990) Peripheral-type benzodiazepine receptors in human glioblastomas pharmacologic characterization of photoaffinity labeling of ligand recognition site. Brain Res 518: 199–208

    Google Scholar 

  12. Dollman CL (1986) Microglia. In: Davis RL, Robertson DM (eds) Textbook of neuropathology. Williams and Wilkins, Baltimore, pp 117–137

    Google Scholar 

  13. Ferrarese C, Appolinio I, Frigo M, Gaini SM, Piolti R, Frattola L (1989) Benzodiazepine receptors and diazepam-binding inhibitor in human cerebral tumors. Ann Neurol 26: 564–568

    Google Scholar 

  14. Ikezaki K, Black KL (1990) Stimulation of cell growth and DNA synthesis by peripheral benzodiazepine. Cancer Letters 49: 115–120

    Google Scholar 

  15. Junck LMD, Olson JMM, Ciliax BJ, Koeppe RA, Watkins GL, Douglas MJ, McKeever PE, Wieland DM, Kilbourn MR, Starosta-Rubinstein S, Mancini WR, Kuhl DE, Greenber HS, Young AB (1989) PET imaging of humain gliomas with ligands for the peripheral benzodiazepine binding site. Ann Neurol 26: 752–758

    Google Scholar 

  16. Mukhin AG, Papadopoulos V, Costa E, Krueger KE (1989) Mitochondrial benzodiazepine receptors regulate steroid biosynthesis. Proc Natl Acad Sci USA 86: 9813–9816

    Google Scholar 

  17. Olson JMM, Junck L, Young AB, Penney JB, Mancini WR (1988) Isoquinoline and peripheral-type benzodiazepine binding in gliomas: implications for diagnostic imaging. Cancer Res 48: 5837–5841

    Google Scholar 

  18. Pappata S, Cornu P, Samson Y, Prenant C, Benavides J, Scatton B, Crouzel C, Hauw JJ, Syrota A (1991) PET study of carbon-11-PK 11195 binding to peripheral type benzodiazepine sites in glioblastoma: a case report. J Nucl Med 32: 1608–1610

    Google Scholar 

  19. Pawilikowski M, Kunert-Radek J, Radek A, Stepien H (1988) Inhibition of cell proliferation of human gliomas by benzodiazepines in vitro. Acta Neurol Scand 77: 231–233

    Google Scholar 

  20. Snyder SH, McEnery MW, Verma A (1990) Molecular Mechanisms of peripheral benzodiazepine receptors. Neurochem Res 15: 119–123

    Google Scholar 

  21. Starosta-Rubinstein S, Ciliax BJ, Penney JB, McKeever P, Young AB (1986) Imaging of a glioma using peripheral benzodiazepine receptor ligands. Proc Natl Acad Sci USA 84: 891–895

    Google Scholar 

  22. Zavala F, Taupin V, Descamps-Latscha B (1991) In vivo treatment with benzodiazepines inhibits murine phagocyte oxidative metabolism and production of interleukin-1, tumour necrosis factor and interleukin-6. J Pharmacol Exp Ther 255: 442–450

    Google Scholar 

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Cornu, P., Benavides, J., Scatton, B. et al. Increase in ω3 (Peripheral-Type Benzodiazepine) binding site densities in different types of human brain tumours. Acta neurochir 119, 146–152 (1992). https://doi.org/10.1007/BF01541799

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