Skip to main content
SpringerLink
Log in

Pharmacokinetics of 11C-labelled BCNU and SarCNU in gliomas studied by PET

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Summary

This paper describes the study of the pharmacodynamics of two 11C-labelled nitrosoureas, 1,3-bis-(2-chloroethyl) nitrosourea (BNCU) and sarcosinamide chloroethylnitrosourea (SarCNU), both labelled in the carbonyl position. Distribution of the radioactivity as measured by positron emission tomography was compared to the distribution of radioactivity observed after injection of 68Ga-EDTA, this being used as an indicator of the blood-brain barrier integrity around the brain tumor. Data suggest that the new nitrosourea, SarCNU, most likely enters brain tissue by different mechanism(s) than BCNU, which enters by diffusion. Data also indicate that use of SarCNU may result in a better tumor to brain ratio than BCNU.

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

References

  1. Kornblith PL, Walker M: Chemotherapy for malignant gliomas. J Neurosurg 68: 1–17, 1988

    Google Scholar 

  2. Walker MD, Alexander E, Jr., Hunt WE, MacCarty CS, Mahaley MS, Mealy J, Norrell HA, Owens G, RansohoffJ, Wilson CB, Gehan EA, Strike TE: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastie gliomas. A cooperative clinical trial. J Neurosurg 49: 333–343, 1978

    Google Scholar 

  3. Walker MD, Green SB, Byar BP, Alexander EJ, Batzdorf U, Brooks WH, Hunt WE, MacCarty CS, Mahaley MS, Jr., Mealey J, Jr., Owens G, Ransohoff J, II, Robertson JT, Shapiro WR, Smith KR, Jr., Wilson CB, Strike TA: Randomized comparisons of radiotherapy and nitrosoureas for malignant glioma after surgery. N Engl J Med 303: 1323–1329,1980

    Google Scholar 

  4. Shapiro WR, Green SB: Re-evaluating the efficacy of intra-arterial BCNU. J Neurosurg 66: 313–315, 1987

    Google Scholar 

  5. Green SB, Byar DP, Walker MD, Pistenmaa DA, Alexander E, Jr., Batzdorf U, Brooks WH, Hunt WE, Mealey J, Jr., Odom GL, Paoletti P, Ransohoff J, II, Robertson JT, Selke RG, Shapiro WR, Smith KR, Jr., Wilson CB, Strike TA: Comparisons of carmustine, procarbazine, and high-dose methylpredmisolone as additions to surgery and radiotherapy for the treatment of malignant glioma. Cancer Treat Rep 67: 121–132, 1983

    Google Scholar 

  6. Schold SC, Shapiro WR, Vick NA, Walker MD: Chemotherapy for malignant gliomas. Ann Neurol 25: 88–89,1989

    Google Scholar 

  7. Levin VA, Kabra PM, Freeman-Dove MA: Pharmacokinetics of intraearotid artery 14C-BCNU in the squirrel monkey. J Neurosurg 48: 587–593, 1978

    Google Scholar 

  8. Fenstermacher JD, Cowles AL: Theoretic limitations of intracarotid infusions in brain tumor chemotherapy. Cancer Treat Rep 61: 519–526, 1979

    Google Scholar 

  9. Diksic M:1986 Theoretical comparison of intra-arterial and intravenous infusion of BCNU (Abstract). Proc 2nd Can Meetings of Neuro-Oncology, June 5–7, 1986, Montreal, Canada

  10. Arnold DL, Shoubridge EA, Feindel W, Villemure J-G: Metabolic changes in cerebral gliomas within hours of treatment with intra-arterial BCNU demonstrated by phosphorus magnetic resonance spectroscopy. Can J Neurol Sci 14: 570–575,1987

    Google Scholar 

  11. Digenis GA, Cheng YC, McQuinn RL, Freed BR, Tilbury RS: 13N labelling of a substituted nitrosourea. Its carbamate and nitrosocarbanyl: In vivo and in vitro studies. In: Root JW, Krohn KA (eds) Short-lived Radionuclides in Chemistry and Biology. American Chemical Society, Washington, 1981, pp 351–367

    Google Scholar 

  12. Feindel W, Diksic M, Yamamoto YL, Arnold D, Shoubridge E, Villemure J-G: Strategies for enhancing drug uptake in gliomas. In: Broggi G, Gerosa MA (eds) Cerebral Gliomas. Elsevier Science Publishers, Amsterdam, 1989, pp 241–250

    Google Scholar 

  13. Suami T, Kato T, Takino H, Hisamatus T: (2-Chloroethyl)-nitrosourea congeners of amino acid amides. J Med Chem 25:829–832,1982

    Google Scholar 

  14. Panasci LC, Dufour M, Chevalier L, Isabel G, Lazarus P, McQuillan A, Arbit E, Brem S, Feindel W: Utilization of HTSCA and CFV-C assay to identify two new 2-chloroethyl-nitrosourea congeners of amino acid amides with increased in vitro activity against human gliomas compared with BCNU. Cancer Chemo Pharm 14: 156–159, 1985

    Google Scholar 

  15. Houchens D, Nies R, Riblets S, Finfrok M, Trigg N: Immunodeficient animals in biochemical research. In: Wu B-Q, Zheng J (eds) VI Int Workshop on Immunodeficient Animals. Karger Publishing, Basel, Switzerland, 1989, pp 157–161

    Google Scholar 

  16. Skalski V, Feindel W, Panasci LC: The cytotoxicity of a 2-chloroethylnitrosourea analog of sarcosinamide in the SK-MG-1 human glioma cell line as a possible indicator for transport. J Neuro-Oncology 7: 189–193, 1989

    Google Scholar 

  17. Thompson CJ, Dagher A, Meyer E, Evans AC: Imaging performance of a dynamic positron tomograph. Positome IIIp. IEEE Trans Med Imaging MI-5: 183–198, 1986

    Google Scholar 

  18. Conway T, Diksic M: Synthesis of ‘no-carrier-added’ carbon-11 SarCNU: The sarcosinamide analog of the chemotherapeutic agent BCNU. J Nucl Med 29: 1957–1960, 1988

    Google Scholar 

  19. Yamamoto LY, Thompson CJ, Meyer E, Robertson JS, Feindel W: Dynamic positron emission tomography for study of cerebral hemodynamics in cross section of head using positron emitting 68Ga-EDTA and 77Kr. J Comput Assist Tomogr 1: 43–56, 1977

    Google Scholar 

  20. Hawkins RA, Phelps ME, Huang S-C, Wapenski JA, Grimm PD, Parker RG, Juillard G, Greenberg P: A kinetic evaluation of blood-brain barrier permeability in human brain tumors with [58Ga]EDTA and positron computed tomography. J Cereb Blood Flow Metab 4: 507–515, 1984

    Google Scholar 

  21. Diksic M, Sako K, Feindel W, Kato A, Yamamoto YL, Farrokhzad S, Thompson CJ: Pharmacokinetics of positron-labelled 1,3-bis(2-chloroethyl)nitrosourea in human brain tumors using positron emission tomography. Canc Res 44: 3120–3124, 1984

    Google Scholar 

  22. Sako K, Diksic M, Farrokhzad S, Yamamoto YL, Feindel W: Pharmacokinetics of 11C-BCNU in experimental brain tumor. J Neuro-Oncol 89: 45–54, 1985

    Google Scholar 

  23. Tyler JL, Yamamoto YL, Diksic M, Théron J, Villemure J-G, Worthington C, Evans AC, Feindel W: Pharmacokinetics of superselective intra-arterial and intravenous [11C]BCNU evaluated by PET. J Nucl Med 27: 775–780, 1986

    Google Scholar 

  24. Gjedde A: Calculation of cerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: a re-examination. Brain Res Rev 4: 237–274, 1982

    Google Scholar 

  25. Patlak CS, Blasberg RG, Fenstermacher JD: Graphical evaluation of blood to brain transfer constants from multiple time uptake data. J Cereb Blood Flow Metab 3: 1–7, 1983

    Google Scholar 

  26. Tyler JL, Diksic M, Villemure J-G, Evans AC, Meyer E, Yamamoto YL, Feindel W: Metabolic and hemodynamic evaluation of gliomas using positron emission tomography. J Nucl Med 28: 1123–1133, 1987

    Google Scholar 

  27. O'Tuama LA, Guilarte TR, Douglass KH, Wagner HN, Jr., Wong DF, Dannals RF, Ravert HT, Wilson AA, LaFrance ND, Bice AN, Links JM: Assessment of [11C]-L methionine transport into the human brain. J Cereb Blood Flow Metab 8: 341–345, 1988

    Google Scholar 

  28. Kirikae M, Diksic M, Yamamoto YL: The transfer coefficients for L-valine and the rate of incorporation of 1-[14C]-valine into proteins in normal adult rat brain. J Cereb Blood Flow Metab 8: 598–605, 1988

    Google Scholar 

  29. Smith CB, Crane AM, Kadekara M, Agranoff BW, Sokoloff L: Stimulation of protein synthesis and glucose utilization in the hypoglossal nucleus induced by axotomy. J Neurosci 4: 2489–2496, 1984

    Google Scholar 

  30. Kirikae M, Diksic M, Yamamoto YL: Quantitative measurements of regional glucose utilization and rate of valine incorporation into brain proteins by double-tracer autoradiography in the rat brain tumor model. J Cereb Blood Flow Metab 9: 87–95, 1989

    Google Scholar 

  31. Shibasaki T, Uki J, Kanoh T, Kawafuchi J-I: Composition of free amino acids in brain tumors. Acta Neurol Scandinav 60: 301–311, 1979

    Google Scholar 

  32. Madajewicz S, West CR, Park HC, Ghoorah J, Avellanosa AM, Takita H, Karakousis C, Vincent R, Caracandas J, Jennings E: Phase II study — intra-arterial BCNU therapy for metastatic brain tumors. Cancer 47: 653–657, 1981

    Google Scholar 

  33. Safdari H, Mampeon B, Dubois JB, Gros C: Intra-arterial 1,3-bis(20-chloroethyl)-1-nitrosourea chemotherapy for the treatment of malignant gliomas of the brain: a preliminary report. Surg Neurol 24: 490–497, 1985

    Google Scholar 

  34. Johnson DW, Parkinson D, Wolpert SM, Kasdeon DL, Kwan ESK, Larcella M, Anderson ML: Intracarotid chemotherapy with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) in 5% dextrose in water in the treatment of malignant glioma. Neurosurg 20: 577–583, 1987

    Google Scholar 

  35. Fenn LG, Wallace W, Yung WKA, Lee YY, Leavens ME, Moser R, Savaraj N, Burgess MA, Plager C, Benjamin RS, Tang RA, Mavligit GM, Field WS: Phase-I trial of intracarotid BCNU and cisplatin in patients with malignant intracerebral tumors. Cancer Drug Delivery 1: 239–245, 1984

    Google Scholar 

  36. Greenberg HS, Ensminger WD, Chandley WF, Layton PB, Junck L, Knake J, Vine AK: Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system. J Neurosurg 61: 423–429, 1984

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

    S. Mitsuki, M. Diksic, T. Conway, Y. L. Yamamoto, J. -G. Villemure & W. Feindel

  2. Hospital and the Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada

    S. Mitsuki, M. Diksic, T. Conway, Y. L. Yamamoto, J. -G. Villemure & W. Feindel

Authors
  1. S. Mitsuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Diksic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Conway
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. L. Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. -G. Villemure
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. W. Feindel
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Work reported here was presented in part at the Symposium on PET and MRS in Oncology, Heidelberg, May 12–14, 1988

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mitsuki, S., Diksic, M., Conway, T. et al. Pharmacokinetics of 11C-labelled BCNU and SarCNU in gliomas studied by PET. J Neuro-Oncol 10, 47–55 (1991). https://doi.org/10.1007/BF00151246

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00151246

Key words

Search

Navigation