Journal of Neuro-Oncology

, Volume 3, Issue 4, pp 397–404 | Cite as

Brain tumor protein synthesis and histological grades: A study by positron emission tomography (PET) with C11-L-Methionine

  • P Bustany
  • M Chatel
  • J M Derlon
  • F Darcel
  • P. Sgouropoulos
  • F Soussaline
  • A Syrota
Article

Summary

Brain protein synthesis may be evaluated in vivo by a PET three compartment methionine model. 14 human brain tumor patients were studied. Protein synthesis rate (PSR) was increased in any glial tumor even in low grades, but this increase was statistically more important in anaplastic tumor.

Radiotherapy action was evaluated in two patients. Local tumoral PSR was reduced to normal brain PSR after treatment. No difference was seen in normal cortex contralateral to the lesion between pre and post radiotherapy examination.

11 C-L-Methionine incorporation measured by PET looks as a very sensitive method for studying tumor metabolism and treatment effects.

Keywords

positron emission tomography brain tumors protein synthesis methionine radiotherapy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hubner KF, Purvis JT, Mahaley SM, Robertson JT, Rogers S, Gibbs WD, King P, Partain CL: Brain tumor imaging by positron emission computed tomography using 11 C-Labeled Amino Acids. J Comp Ass Tom 6(3):544–550, 1982.Google Scholar
  2. 2.
    Ackerman RH, Davis SM, Correia JA, Alpert NM, Buonanno F, Finkelstein S, Brownell GL, Traveras JM: Positron imaging of CBF and metabolism in patients with cerebral neoplasm. J Cer Blood Flow Met suppl 1, 1:575–576, 1981.Google Scholar
  3. 3.
    Di Chiro G, Oldfield E, Bairamian D, Patronas NJ, Brooks RA, Mansi L, Smith BH, Kornblith PL, Margolius RJ: Comp Ass Tom 7(6):937–945, 1983.Google Scholar
  4. 4.
    Rhodes CG, Wise RJ, Gibbs JM, Frackowiak RSJ, Hatazawa J, Palmer AL, Thomas DGT, Jones T: In vivo distrubances of the oxidative metabolism of glucose in human cerebral gliomas. Ann Neurol 14:614–626, 1983.Google Scholar
  5. 5.
    Bustany P, Sargent T, Saudubray JM, Henry JF, Comar D: Regional human brain uptake and protein incorporation of 11 C-L-Methionine studied in vivo with PET J Cer Blood Flow Met suppl 1, 1:517–518, 1981.Google Scholar
  6. 6.
    Bustany P, Comar D: Protein synthesis evaluation in brain and other organs in human by PET. In: Reirich M et al (eds) Position Emission Tomography. Alan R. Liss New York: 183–201, 1985.Google Scholar
  7. 7.
    Kozik M, Ozarewska AE: Autoradiographic studies on methionine — 3 H incorporation into rat brain. Exp path Bd 9, 5:274–279, 1974.Google Scholar
  8. 8.
    Osuji GO: An oscillatory mechanism for the glutamyl transpeptidase-mediated translocation of amino-acids across the cell membrane. J Theor Biol 109:1–15, 1984.Google Scholar
  9. 9.
    Oldendorf WA: Brain uptake of radiolabeled amino-acids, amines, and hexoses after arterial injection. Am J Physiol 221(6):1629–1639, 1971.Google Scholar
  10. 10.
    Langer BW: Organ and intracellular location of the methionine methyl group synthetizing system of the rat. Proc Soc Exp Biol Med 115:1088–1090, 1984.Google Scholar
  11. 11.
    Barak AJ, Beckenhauer HC, Tuma DJ: Use of S-Adenosylmethionine as an index of methionine recycling in rat liver slices. Analytical Biochemistry 127:372–375, 1982.Google Scholar
  12. 12.
    Merei FT, Gallyas F: Quantitative determination on the uptake of (35 S) methionine in different regions of the normal rat brain. J Neurochem 11:257–264, 1964.Google Scholar
  13. 13.
    Blomstrand C, Hamberger A: Protein turnover in cell-enriched fractions from rabbit brain. J Neurochem 16:1401–1407, 1969.Google Scholar
  14. 14.
    Wheatley DN: On the problem of linear incorporation of amino acids into cell proteins. Experienta 38:818–820, 1982.Google Scholar
  15. 15.
    Stern PH, Wallace CD, Hoffman RM: Altered methionine metabolism occurs in all members of a set of diverse human tumor cell lines. J Cell Phys 119:29–34, 1984.Google Scholar
  16. 16.
    Tisdale MJ: Utilization of performed and endogenously synthetized methionine by cells in tissue culture. Br J Cancer 49:315–320, 1984.Google Scholar
  17. 17.
    Gaitonde MK, Richter D: The metabolism of 35 S-methionine in the brain. In: Richter D (ed.) Metabolism of the Nervous System Pergamon Press. New York, 1958, 449–455.Google Scholar
  18. 18.
    Mudd SH, Finkelstein JD, Irreverre F, Laster L: Transsulfuration in mammals: microassays and tissue distribution of three enzymes of the pathways. J Biol Chem 240, 11:4382–4392, 1965.Google Scholar
  19. 19.
    Benesh FC, Carl GF: Methyl biogenesis in biological psychiatry. Biol Psych 13(4):465–480, 1978.Google Scholar
  20. 20.
    Rassin DK, Gaull GE: Subcellular distribution of enzymes of transmethylation and transsulphuration of rat brain. J neurochem 24:969–978, 1975.Google Scholar
  21. 21.
    Hiemke C, Rudiger G: Regional distribution of methionine adenosyltransferase in rat brain as measured by a rapid radiochemical method. J Neurochem 37, 3:613–618, 1981.Google Scholar
  22. 22.
    Bustany P, Henry JF, Soussaline F, Comar D: Brain protein synthesis in normal emission tomography with 11 C-L-Methionine. In: Magistretti PL (ed.) Functional Radionuclide imaging of the brain. Raven Press New-York 319–324, 1983.Google Scholar
  23. 23.
    Soussaline F, Todd-Pokropek AE, Plummer D, Comar D, Loch C, Houle S, Kellershohn C: The physical performances of a single slice positron tomography system and preliminary results in a clinical environnement. Eur J Nucl Med 4:237–249, 1979.Google Scholar
  24. 24.
    Comar D, Cartron JC, Maziere M, Marazano C: Labelling and metabolism of methionine methyl-11 C. Eur J Nucl Med 1:11–14, 1976.Google Scholar
  25. 25.
    Vallabhajosula S, Goldsmith SJ, Lipszyc H, Chahinian AP, Ohnuma T: 67 Ga-transferrin and 67 Ga-lactoferrin binding to tumor cells: specific versus non specific glycoprotein-cell interaction. Eur J Nucl Med 8:354–357, 1983.Google Scholar
  26. 26.
    Hayes RL: The interaction of gallium with biological systems. In J Nucl Med Biol 10(4):257–261, 1983.Google Scholar
  27. 27.
    Loch C, Maziere B, Comar D: A new generator for ionic gallium 68. J Nucl Med 21:171–173, 1980.Google Scholar
  28. 28.
    Maziere B, Loch C, Ricordel Y, Comar D: Regional cerebral blood pool measurements using 68 Ga labeled proteins. In: Raynaud C (ed.) Nuclear Medicine and Biology vol. 1. Pergamon Press: 666–669, 1982.Google Scholar
  29. 29.
    Larsen OA, Lassen AL: Cerebral hematocrit in normal man. J Appl Physiol 19, 4:571–574, 1964.Google Scholar
  30. 30.
    Oldendorf WH, Kitano M, Shimizu S, Oldendorf S: Hematocrit of the human cranial blood pool. Circ Res 17:532–539, 1965.Google Scholar
  31. 31.
    Phelps ME, Hoffman EJ, Coleman RE, Welch MJ, Raichle ME, Weiss ES, Sobel BE, Ter-Pogossian MM: Tomographic images of blood pool and perfusion in brain and heart. J Nucle Med 17:603–612, 1976.Google Scholar
  32. 32.
    Hagenfeldt L, Arivdsson A: The distribution of amino-acids between plasma and erythrocytes. Clinica Chimica Acta 100:233–141, 1980.Google Scholar
  33. 33.
    Young JD, Jones SEM, Ellory JC: Amino-acids transport in human and in sheep erythrocytes. Proc R Soc Lond B 209:355–375, 1980.Google Scholar
  34. 34.
    Grubb RL, Raichle ME, Eichling JO, Ter-Pogossian MM: The effects of changes in Pa CO22 on cerebral blood volume, blood flow and vascular mean transit time. Stroke 5:630–639, 1974.Google Scholar
  35. 35.
    Newmark ME, Theodore WH, Sato S, De La Paz R, Patronas N, Brooks R, Jabbari B, Di Chiro G: EEG, transmission computed tomography and positron emission tomography with fluorodeoxyglucose 18 F. Their use in adults with gliomas. Arch Neurol 40:607–610, 1983.Google Scholar
  36. 36.
    Bustany P, Henry JF, De Rotrou J, Signoret P, Cabanis E, Zarifian E, Ziegler M, Derlon JM, Crouzel C, Soussaline F, Comar D: Correlations between clinical state and positron emission tomography measurements of local brain protein synthesis in Alzheimer's dementia, Parkinson's disease, schizophrenia and gliomas. In: Greitz T et al. (eds) the metabolism of the human brain studied with positron. Raven Press New York: 241–248, 1985.Google Scholar
  37. 37.
    Hoffman RM, Erbe RW: High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine. Proc Natl Acad Sci USA 73, 5:1523–1527, 1976.Google Scholar
  38. 38.
    Rieth KG, Di Chiro G, London WT, Sever JL, Houff SA, Kornblith PL, Mc Keever PE, Buonomo C, Padgett BL, Walker DL: Experimental glioma in primates: a computed tomography model. J Comp Ass Tom 4, 3:285–290, 1980.Google Scholar
  39. 39.
    Front D, Israel O, Kohn S, Nir I. The blood tissue barrier of human brain tumors: correlation of scintigraphic and ultrastructural findings: concise communication. J Nucl Med 25:461–465, 1984.Google Scholar
  40. 40.
    Groothuis DR, Vick NA: Brain tumors and the blood-brain barrier. TINS July, 232–235, 1982.Google Scholar
  41. 41.
    Patronas N, Di Chiro G, Broocks RA, De Lapaz RL, Kornblith PL, Smith BH, Rizzoli HV, Kessler RM, Manning RG, Charming M, Wolf AP, O'Connor CM: Work in progress: (18 F) fluorodeoxyglucose and positron emission tomography in the evaluation of radiation necrosis of the brain. Radiology, 144:885–889, 1982.Google Scholar

Copyright information

© Martinus Nijhoff Publishers 1986

Authors and Affiliations

  • P Bustany
    • 1
    • 4
  • M Chatel
    • 2
  • J M Derlon
    • 3
  • F Darcel
    • 2
  • P. Sgouropoulos
    • 2
  • F Soussaline
    • 1
  • A Syrota
    • 1
  1. 1.Service Hospitalier F Joliot, CEA Dept de BiologieHôpital ArchangéOrsay
  2. 2.Service de NeurologieCentre Hospitalier UniversitaireRennes
  3. 3.Service de NeurochirurgieCentre Hospitalier UniversitaireCaen
  4. 4.Laboratoire de pharmacologieCentre Hospitalier UniversitaireCaen

Personalised recommendations