Distribution of etanidzole into human brain tumors: Implications for treating high grade gliomas

Selwyn J. Hurwitz, C. Norman Coleman, Nancy Riese, Jay S. Loeffler, Eben Alexander, Lori Buswell, Tamlyn Yee Neben, Leon Sahargel, Robert A. Kramer

Research output: Contribution to journalArticle

Abstract

Etanidazole was developed as an oxygen-mimetic radiosensitizer less lipophilic than misonidazole. Sensitization depends on an adequate concentration of drug in the tumor at the time of irradiation. Therefore, due to the presence of the blood-brain barrier, brain tumors may theoretically be difficult to radiosensitize due to the hydrophilic characteristics of etanidazole. Based on previous reports of loss of BBB integrity in brain tumors, we investigated the ability of etanidazole to penetrate into malignant gliomas of patients receiving etanidazole as part of a Phase I continuous infusion protocol. The patients had completed previous external beam irradiation. Twenty-two patients were studied and their etanidazole plasma and biopsy data were compared to the 2-compartment model derived from a second group of 19 patients with bolus etanidazole. Etanidazole concentration in brain tumor biopsies varied widely and appeared to be clustered into a higher and a lower pharmacokinetic group having mean tumor to well-perfused second compartment ratios of 1 and 0.25, respectively. Both high and low etanidazole concentrations were evident in different biopsies obtained from the same patient. Correlations between histology and tissue concentrations suggested that the higher level correspond to malignant tissue. These data indicate that the blood brain barrier is disrupted to varying degrees by the brain tumor and/or prior irradiation and that etanidazole penetrates into brain tumors.

Original languageEnglish (US)
Pages (from-to)573-576
Number of pages4
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume22
Issue number3
DOIs
StatePublished - 1992
Externally publishedYes

Fingerprint

Etanidazole
Brain Neoplasms
Glioma
brain
grade
tumors
blood-brain barrier
compartments
irradiation
Blood-Brain Barrier
Biopsy
histology
Misonidazole
integrity
low concentrations
drugs
Neoplasms
Histology
Pharmacokinetics

Keywords

  • 2-nitroimidazoles
  • Brachytherany
  • Brain tumors
  • Chemical modifiers
  • Continuous infusion
  • Etanidazole
  • Hypoxic cell sensitizers
  • Radiosensitizers
  • SR 2508

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Hurwitz, S. J., Norman Coleman, C., Riese, N., Loeffler, J. S., Alexander, E., Buswell, L., ... Kramer, R. A. (1992). Distribution of etanidzole into human brain tumors: Implications for treating high grade gliomas. International Journal of Radiation Oncology, Biology, Physics, 22(3), 573-576. https://doi.org/10.1016/0360-3016(92)90879-M

Distribution of etanidzole into human brain tumors : Implications for treating high grade gliomas. / Hurwitz, Selwyn J.; Norman Coleman, C.; Riese, Nancy; Loeffler, Jay S.; Alexander, Eben; Buswell, Lori; Yee Neben, Tamlyn; Sahargel, Leon; Kramer, Robert A.

In: International Journal of Radiation Oncology, Biology, Physics, Vol. 22, No. 3, 1992, p. 573-576.

Research output: Contribution to journalArticle

Hurwitz, SJ, Norman Coleman, C, Riese, N, Loeffler, JS, Alexander, E, Buswell, L, Yee Neben, T, Sahargel, L & Kramer, RA 1992, 'Distribution of etanidzole into human brain tumors: Implications for treating high grade gliomas', International Journal of Radiation Oncology, Biology, Physics, vol. 22, no. 3, pp. 573-576. https://doi.org/10.1016/0360-3016(92)90879-M
Hurwitz, Selwyn J. ; Norman Coleman, C. ; Riese, Nancy ; Loeffler, Jay S. ; Alexander, Eben ; Buswell, Lori ; Yee Neben, Tamlyn ; Sahargel, Leon ; Kramer, Robert A. / Distribution of etanidzole into human brain tumors : Implications for treating high grade gliomas. In: International Journal of Radiation Oncology, Biology, Physics. 1992 ; Vol. 22, No. 3. pp. 573-576.
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