Skip to main content
SpringerLink
Log in

Murine sarcoma virus-induced brain tumors

Concurrent measurements of blood flow and transcapillary transport

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

Summary

Intracerebral inoculation of Murine Sarcoma Virus (MSV) into rats induces highly vascular brain tumors. Blood flow, F, and a unidirectional blood-to-tissue transfer constant, K, were measured concurrently in 16 separate brain tumors in 13 rats. Regional measurements of F and K were obtained using double-label quantitative autoradiography with 131I-iodoantipyrine, 14C-alpha aminoisobutyric acid, and computerized microdensitometry with image analysis. Regional tissue extraction fractions (E) were calculated for different brain and tumor regions. The following observations were made: (1) intracerebral inoculation of MSV in rats of different ages produced a single histologic tumor type (angiosarcoma), although tumor yield decreased and latency increased when older rats were inoculated; (2) whole tumor blood flow values averaged 63.9 ± 20.9 (SD) ml hg−1 min−1, less than F of tumor-free gray matter; (3) the mean value of the transfer constant was 1.19 ± 0.84 ml hg−1 min−1, 5 times the value in contralateral tumor-free brain; (4) moderate regional variation of F and K values were observed within each tumor, with increased K values extending into the regions of brain around tumor; (5) mean extraction fractions (E) of AIB for whole tumor were low (range = 0.0021 to 0.08), with a distinct and decreasing gradient from tumor center to BAT; (6) there was poor correlation between F, K and E values, and tumor histology, including regions that microscopically appeared highly vascular; (7) in most regions of the MSV-induced brain tumors, capillary permeability and/ or surface area seem to be determinant in blood-to-tissue transport processes.

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. Groothuis DR, Blasberg RG, Molnar P, Bigner DD, Fenstermacher JD: Regional blood flow in avian sarcoma virus (ASV)-induced brain tumors. Neurology (Cleveland) 33: 686–696, 1983.

    Google Scholar 

  2. Molnar P, Blasberg RG, Groothuis DR, Bigner DD, Fenstermacher JD: Regional blood-to-tissue transport in avian sarcoma virus (ASV)-induced brain tumors. Neurology (Cleveland) 33:702–711, 1983.

    Google Scholar 

  3. Groothuis DR, Pasternak JF, Fischer JM, Bigner DD, Blasberg RG, Vick NA: Measurement of regional blood flow in RG-2 experimental brain tumors. Cancer Research 43: 3362–3367, 1983.

    Google Scholar 

  4. Groothuis DR, Fischer JM, Pasternak JF, Bigner DD, Blasberg RG, Vick NA: Regional measurements of blood-to-tissue transport in experimental RG-2 rat gliomas. Cancer Research 43:3368–3373, 1983.

    Google Scholar 

  5. Blasberg RG, Kobayashi T, Horowitz M, Rice J, Groothuis D, Molnar P, Fenstermacher JD: Regional blood flow in ethylnitrosourea (ENU)-induced brain tumors. Ann Neurology 14:189–201, 1983.

    Google Scholar 

  6. Blasberg RG, Horowitz M, Rice J, Groothuis DR, Molnar P, Fenstermacher JD: Regional blood-to-tissue transport in ethylnitrosourea (ENU)-induced tumors. Ann Neurology 14:202–215, 1983.

    Google Scholar 

  7. Groothuis DR, Molnar P, Blasberg RG: Regional blood flow and blood-to-tissue transport in five brain tumor models: Implications for chemotherapy. In: Rosenblum M and Wilson CB (eds), Progress in experimental tumor research, Vol 27. S Karger, Basel, 1984, pp 132–153.

    Google Scholar 

  8. Butler AR, Horii SC, Kricheff II, Shannon MB, Budzilovich GN: Computed tomography in astrocytomas: A statistical analysis of the parameters of malignancy and the positive contrast-enhanced CT scan. Radiology 129:433–439, 1978.

    Google Scholar 

  9. Takeda N, Tanaka R, Nakai O, Veki K: Dynamics of contrast enhancement in delayed computed tomography of brain tumors: Tissue-blood ratio and differential diagnosis. Radiology 142:663–668, 1982.

    Google Scholar 

  10. DiChiro G, DeLaPaz RL, Brooks RA, Sokoloff L, Kornblith PL, Smith BH, Patronas NJ, Kufta CV, Kessler RM, Johnston GS, Manning RG, Wolf AP: Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography. Neurology (Cleveland) 32: 1323–1329, 1982.

    Google Scholar 

  11. Ito M, Lammertsma AA, Wise RJS, Bernardi S, Frackowiak RSJ, Heather JD, McKenzie CG, Thomas DGT, Jones T: Measurement of regional cerebral blood flow and oxygen utilisation in patients using 15O and positron emission tomography: Analytical techniques and preliminary results. Neuroradiology 23:63–74, 1982.

    Google Scholar 

  12. Yung WK, Blank NK, Vick NA: Glioblastoma: Induction of a reproducible autochonous tumor in rats with murine sarcoma virus. Neurology (Cleveland) 26:76–83, 1976.

    Google Scholar 

  13. Pitts OM, Powers JM, Hoffman PM: Vascular neoplasms induced in rodent central nervous system by murine sarcoma viruses. Lab Investigation 49:171–182, 1983.

    Google Scholar 

  14. Blasberg RG, Groothuis DR, Molnar P: The application of quantitative autoradiographic measurements in experimental brain tumors. Seminars in Neurology 1:203–223, 1981.

    Google Scholar 

  15. Blasberg RG, Gazendam J, Patlak CS, Shapiro WS, Fenstermacher JD: Changes in blood-brain transfer parameters induced by hyperosmolar intracarotid infusion and by metastatic tumor growth. In: Eisenberg HM and Suddith RL (eds), The cerebral microvasculature. Plenum Publ. Corp, New York 1980, pp 307–319.

    Google Scholar 

  16. Blasberg RG, Molnar P, Groothuis DR, Patlak C, Owens E, Fenstermacher JD: Concurrent measurements of blood flow and transcapillary transport in ASV-induced experimental brain tumors: Implications for brain tumor chemotherapy. J Pharmacology Experimental Therapeutics (in press)

  17. Goochee C, Rasband W, Sokoloff L: Computerized densitometry and color coding of [14C] deoxyglucose autoradiographs. Ann Neurol 7: 359–370, 1980.

    Google Scholar 

  18. Blasberg RG, Patlak CS, Fenstermacher JD: The transport of alpha-aminoisobutyric acid across brain capillary and cellular membranes and the quantification of changes in blood-brain barrier permeability. J Cerebral Blood Flow Metabolism 3:8–32, 1983.

    Google Scholar 

  19. Groothuis DR, Fross RD, Molnar P, Pasternak JF, Blasberg RG, Patlak C, Vick, NA: Applicability of multipletime-point measurements for in vivo determination of blood to-tissue transfer constants of iothalamate meglumine and AIB in experimental gliomas. J Cerebral Blood Flow Metabolism 3(Suppl 1):S93-S94, 1983.

    Google Scholar 

  20. Kety SS: The theory and application of the exchange of inert gas at the lungs and tissue. Pharmacol Rev 3:1–41, 1959.

    Google Scholar 

  21. Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L: Measurement of local cerebral blood flow with iodo[14C]antipyrine. Am J Physiol 3:56–66, 1978.

    Google Scholar 

  22. Blasberg RG, Molnar P, Groothuis DR, Patlak C, Fenstermacher JD: Simultaneous measurements of blood flow and relative glucose utilization in ASV-induced brain tumors. J Cerebral Blood Flow Metabolism 1(Suppl1):S68-S69, 1981.

    Google Scholar 

  23. Fenstermacher JD, Blasberg RG, Patlak CS: Methods for quantifying the transport of drugs across brain barrier systems. Pharmacol Ther 14:217–248, 1981.

    Google Scholar 

  24. Blasberg RG, Molnar P, Horowitz M, Kornblith P, Pleasants R, Fenstermacher JD: Regional blood flow in RT-9 tumors. J Neurosurg 58: 863–873, 1983.

    Google Scholar 

  25. Blasberg RG, Kobayashi T, Patlak CS, Shinohara M, Miyaoka M, Rice JM: Regional blood flow, capillary permeability, and glucose utilization in two brain tumor models: Preliminary observations and pharmacokinetic implications. Cancer Treat Rep 65(suppl2):3–12, 1981.

    Google Scholar 

  26. Molnar P, Blasberg RG, Horowitz M, Smith B, Fenstermacher JD: Regional blood-to-brain transport in RT-9 brain tumors. J Neurosurg 58:874–884, 1983.

    Google Scholar 

  27. Renkin EM: Transport of potassium-42 from blood-to-tissue in isolated mammalian skeletal muscle. Am J Physiol 197:1205–1210, 1959.

    Google Scholar 

  28. Crone C: The permeability of capillaries in various organs as determined by the use of the ‘indicator diffusion’ method. Acta Physiol Scand 58:292–305, 1963.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Northwestern University Evanston Hospital, 60201, Evanston, IL, USA

    Francine J Vriesendorp, Dennis R Groothuis & Nicholas A Vick

Authors
  1. Francine J Vriesendorp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dennis R Groothuis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicholas A Vick
    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

Vriesendorp, F.J., Groothuis, D.R. & Vick, N.A. Murine sarcoma virus-induced brain tumors. J Neuro-Oncol 2, 301–314 (1984). https://doi.org/10.1007/BF00178113

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00178113

Keywords

Search

Navigation