Skip to main content
SpringerLink
Log in

Permeability change and brain tissue damage after intracarotid administration of cisplatin studied by double-tracer autoradiography in rats

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

Summary

The present study was designed to find the reliable parameter(s) for the detection of early neurotoxicity following intracarotid (IC) administration of cisplatin. IC administration was performed for 60 minutes in female Wistar rats derived into four groups according to the dose given (1 mg, 1.2 mg, and 1.5 mg of cisplatin, and normal saline in control rats). Blood-brain barrier (BBB) permeability and local cerebral blood flow (LCBF) were measured by a double-tracer autoradiography technique using 1-[14 C]-α-aminoisobutyric acid (14 C-AIB) and 4-[18 F] fluoroantipyrine (18 F-FAP), respectively. Blood chemistry and neuropathology were also examined. BBB permeability was incereased only on the ipsilateral side. This increase was dose-dependent, preceded the brain necrosis, and was statistically significant in the hypothalamus [1.2 mg group), auditory cortex and caudoputamen (1.5 mg group). Renal dysfunction was often observed. The changes in the LCBF did not occur until brain necrosis was noticeable. These findings demonstrate that the increase in the BBB permeability provides a sensitive and reliable indication of an early toxicity to brain tissue following IC administration of cisplatin.

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. Fenstermacher JD, Cowles AL: Theoretic limitation of intracarotid infusion in brain tumor chemotherapy. Cancer Treat Rep 61(4): 519–526, 1977

    PubMed  Google Scholar 

  2. Blasberg RG: Pharmacodynamics and the blood-brain barrier. Natl Cancer Inst Monogr 46: 19–27, 1977

    PubMed  Google Scholar 

  3. Feun LG, Wallace S, Stewart DJ, Chuang V, Yung WKA, Leavens ME, Burgess MA, Savaraj N, Benjamin RS, Young SE, Tang RA, Handy S, Mavlight G, Fields WS: Intracarotid infusion of cis-diamminedichloroplatinum in the treatment of recurrent malignant brain tumors. Cancer 54: 794–799, 1983

    Google Scholar 

  4. Lehane DE, Bryan RN, Horowitz B, DeSantos L, Ehni G, Zubler MA, Moiel R, Rudolph L, Aldama-Leubbert A, Mahoney D, Harper R: Intraarterial cis-platinum chemotherapy for patients with primary and metastatic brain tumors. Cancer Drug Deliv 1: 69–77, 1983

    PubMed  Google Scholar 

  5. Stewart DJ, Wallace S, Feun L, Leavens M, Young SL, Handel S, Mavlight G, Benjamin RS: A phase I study of intracarotid artery infusion of cis-diamminedichloroplatinum (II) in patients with recurrent malignant intracerebral tumors. Cancer Res 42: 2059–2062A, 1982

    PubMed  Google Scholar 

  6. Calvo FA, Pastor MA, Dy C, Alegria E, Aparicio LMA: Intra-arterial and intravenous chemotherapy for the treatment of malignant glioma. Am J Clin Oncol 8: 200–209, 1985

    PubMed  Google Scholar 

  7. Newton HB, Page MA, Junck L, Greenberg HS: Intra-arterial cisplatin for the treatment of malignant gliomas. J Neuro-Oncol 7: 39–45, 1989

    Google Scholar 

  8. Mahaley MS, Hipp SW, Dropcho EJ, Bertsch L, Cush S, Tirey T, Gillespie Y: Intracarotid cisplatin chemotherapy for recurrent gliomas. J Neurosurg 70: 371–378, 1989

    PubMed  Google Scholar 

  9. Sciki Y, Shibata I, Terao H, Kudo M, Noguchi T: Pharmacokinetic study of selective continuous-internal carotid CDDP infusion in malignant brain tumors. Neurol Med Chir (Tokyo) 31: 695–701, 1991

    Google Scholar 

  10. Ichimura K, Ohno K, Hoyagi M, Tamaki M, Suzuki R, Hiratowa K: Capillary permeability in experimental rat glioma and effects of intracarotid CDDP administration on tumor drug delivery. J Neuro-Oncol 16: 211–215, 1993

    Google Scholar 

  11. Stewart DJ, Benjamin RS, Zimmerman S, Caprioli RM, Wallace S, Chuang V, Calvo III D, Samuels M, Bonura J, Loo TL: Clinical pharmacology of intra-arterial cis-diamminedichloroplatinum (II). Cancer Res 43: 917–920, 1983

    PubMed  Google Scholar 

  12. Kapp JP, Vance RB: Supraophthalmic carotid infusion for recurrent glioma. Rationale, technique, and preliminary results for cisplatin and BCNU. J Neuro-Oncol 3: 5–11, 1985

    Google Scholar 

  13. Kapp JP, Sanford RA: Neurological deficit after carotid infusion of cisplatin and 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) for malignant glioma: an analysis of risk factors. Neurosurgery 19: 779–783, 1986

    PubMed  Google Scholar 

  14. Saris SC, Wright DC, Oldfield EH, Blasberg RG: Intravascular streaming and variable delivery to brain following carotid artery infusion in the Sprague-Dawley rat. J Cereb Blood Flow & Metab 8: 116–120, 1988

    Google Scholar 

  15. Blacklock JB, Wright DC, Dedrick RL, Blasberg RG, Lutz RJ, Doppman JL, Oldfield EH: Drug streaming during intra-arterial chemotherapy. J Neurosurg 64: 284–291, 1986

    PubMed  Google Scholar 

  16. Lutz RJ, Dedrick RL, Boretos JW, Oldfield EH, Blacklock JB, Doppman JL: Mixing studies during intracarotid artery infusions in anin vitro model. J Neurosurg 64: 277–283, 1986

    PubMed  Google Scholar 

  17. Sako K, Kato A, Diksic M, Tamamoto YL: Use of short-lived18 F and long-lived14 C in double tracer autoradiography for simultaneous measurement of LCBF and LCGU. Stroke 15: 896–900, 1984

    PubMed  Google Scholar 

  18. Sako K, Diksic M, Yamamoto YL, Feindel W: Evaluation of [18 F]F-4-fluoroantipyrine as a new blood flow tracer for multiradionuclide autoradiography. J Cereb Blood Flow & Metab 4: 259–263, 1984

    Google Scholar 

  19. Blasberg RG, Fenstermacher JD, Patlack CS: Transport of α-aminoisobutyric acid across brain capillary and cellular membranes. J Cereb Blood Flow & Metab 3: 215–225, 1983

    Google Scholar 

  20. Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L: Measurement of local cerebral blood flow with iodol (14 C) antipyrine. Am J Physiol 234: H59-H66, 1978

    PubMed  Google Scholar 

  21. Lange RC, Spencer RP, Harder HC: Synthesis and distribution of a radiolabelled antitumor agent: cis-diamminedichloroplatinum (II). J Nucl Med 13: 328–330, 1972

    PubMed  Google Scholar 

  22. Litterst CL, LeRoy AF, Guarino AM: Disposition and distribution of platinum following parenteral administration of cis-dichlorodiammineplatinum (II) to animals. Cancer Treat Rep 63: 1485–1492, 1979

    PubMed  Google Scholar 

  23. Kociba RJ, Sleight SD: Acute toxicologic and pathologic effect of cis-diamminedichloroplatinum (NCS-119875) in the male rat. Cancer Chemotherapy Reports 55: 1–8, 1971

    Google Scholar 

  24. Stewart DJ, Leavens M, Maor M, Feun L, Luna M, Bonura J, Caprioli R, Loo TL, Benjamin RS: Human central nervous system distribution of cis-diamminedichloroplatinum and use as a radiosensitizer in malignant brain tumors. Cancer Research 42: 2474–2479, 1982

    PubMed  Google Scholar 

  25. Ginos JZ, Cooper AJL, Dhawan V, Lai JCK, Strother SC, Alcock N, Rottenberg DA: (13 N) cisplatin PET to assess pharmacokinetics of intra-arterial versus intravenous chemotherapy for malignant brain tumors. J Nucl Med 28: 1844–1852, 1987

    PubMed  Google Scholar 

  26. Neuwelt EA, Glasberg M, Frenkel E, Barnett P: Neurotoxicity of chemotherapeutic agents after blood-brain modification: neuropathological studies. Ann Neurol 14: 316–324, 1983

    PubMed  Google Scholar 

  27. Ward JM, Fauvie KA: The nephrotoxic effects of cis-diamminedichloroplatinum (II) (NSC-119875) in male F344 rats. Toxicol Appl Pharmacol 38: 535–547, 1976

    PubMed  Google Scholar 

  28. Spigelman MK, Zappula RA, Johnson J, Goldsmith SJ, Malis LI, Holland JF: Etoposide-induced blood-brain barrier disruption. J Neurosurg 61: 674–678, 1984

    PubMed  Google Scholar 

  29. Phillips PC, Thaler HT, Berger CA, Fleisher M, Wellner D, Allen JC, Rottenberg DA: Acute high-dose methotrexate neurotoxocity in the rat. Ann Neurol 20: 583–589, 1986

    PubMed  Google Scholar 

  30. Phillips PC, Dhawan V, Strother SC, Sidtis JJ, Evance AC, Allen JC, Rottenberg DA: Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy. Ann Neurol 21: 59–63, 1987

    PubMed  Google Scholar 

  31. Gouyette A, Apchin A, Foka M, Richard J-M: Pharmacokinetics of intra-arterial and intravenous cisplatin in head and neck cancer patients. Eur J Cancer Clin Oncol 22: 257–263, 1986

    PubMed  Google Scholar 

  32. Gormley PE, Bull JM, LeRoy AF, Cysyk P: Kinetics of cisdichlorodiammineplatinum. Clin Pharmacol Ther 25: 351–357, 1979

    PubMed  Google Scholar 

  33. Vermorken JB, Vijgh WJFVD, Klein I, Hart AAM, Gall HE, Pinedo HM: Pharmacokinetics of free and total platinum species after short-term infusion of cisplatin. Cancer Treat Rep 68: 505–515, 1984

    PubMed  Google Scholar 

  34. Degregorio MW, King OY, Holleran WM, Wilbur BJ, Cadman EC, Deisseroth AB, Wilbur JR: Ultra filtrate and total platinum in plasma and cerebrospinal fluid in a patient with neuroblastoma. Cancer Treat Rep 69: 1441–1442, 1985

    PubMed  Google Scholar 

  35. Madias NE, Harrington JT: Platinum nephrotoxicity. Am J Medicine 65: 307–314, 1978

    Google Scholar 

  36. Leonard B, Eccleston E, Jones D, Todd P, Walpole A: Antileukemic and nephrotoxic properties of platinum compounds. Nature 234: 43–45, 1971

    PubMed  Google Scholar 

  37. Klatzo I, Suzuki R, Orzi F, Schuier F, Nitsch C: Mechanisms of ischemic brain edema. In: Recent Progress in the Study and Therapy of Brain Edema. Go KG, Baathmann A (Eds.) Plenum Press, NY. pp 1–10, 1982

    Google Scholar 

  38. Steinwall O, Klatzo I: Selective vulnerability of the bloodbrain barrier in chemically induced lesions. J Neuropathol Exp Neurol 25: 542–559, 1966

    PubMed  Google Scholar 

  39. Sokoloff L, Reivich M, Kennedy C, Rosiers HD, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M: The14C-deoxyglucose method for the measurement of local glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897–910, 1977

    PubMed  Google Scholar 

  40. Kato A, Diksic M, Yamamoto YL, Strother SC, Feindel W: An improved approach for measurement of regional cerebral rate constants in deoxyglucose method with positron emission tomography. J Cereb Blood Flow Metab 4: 555–563, 1984

    PubMed  Google Scholar 

  41. Schmall B, Conti PS, Bigler BE, Zanzonico PB, Reiman RE, Benua RS, Yeh SD, Dahl JR, Lee R, Laughlin JS: Imaging studies of patients with malignant fibrous histiocytoma using11 C-alpha-aminoisobutiric acid (AIB). Clin Nucl Med 12: 22–26, 1987

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cone Laboratory Neurosurgical Research and Neuroisotope Laboratory, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

    Shinji Sugimoto, Y Lucas Yamamoto, Shinji Nagahiro & Mirko Diksic

Authors
  1. Shinji Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Lucas Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shinji Nagahiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mirko Diksic
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Dr. S. Sugimoto was on leave of absence from the Department of Neurosurgery, School of Medicine, Hokkaido University N15W7, Kita-Ku, Sapporo, Japan

Dr. S. Nagahiro was on leave of absence from the Department of Neurosurgery, Kumamoto University, Medical School, 1-1-1 Honjyo, Kumamoto, 860 Japan

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sugimoto, S., Yamamoto, Y.L., Nagahiro, S. et al. Permeability change and brain tissue damage after intracarotid administration of cisplatin studied by double-tracer autoradiography in rats. J Neuro-Oncol 24, 229–240 (1995). https://doi.org/10.1007/BF01052839

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01052839

Key words

Search

Navigation