Further characterization of 4-bromomisonidazole as a potential detector of hypoxic cells

J. S. Rasey, Kenneth Krohn, Z. Grunbaum, P. J. Conroy, K. Bauer, R. M. Sutherland

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

[14C]Bromomisonidazole was prepared by direct bromination of [ring-2] [14C]misonidazole in dioxane. The uptake and binding of the two labeled sensitizers were compared in vitro in 1-mm EMT-6 spheroids which contain a necrotic core. Using liquid scintillation counting it was shown that spheroids incubated with 50 μM [14C]bromomisonidazole concentrated drug above levels in the medium by 1 1/2 hr and achieved maximum concentration by 10 hr with no further increase at 23 hr. Spheroids incubated with 50 μM [14C]misonidazole may concentrate the sensitizer more slowly but ultimately reached the same fivefold increase over levels in the medium by 23 hr as was observed for bromomisonidazole. Autoradiographs prepared from spheroids after incubation with [14C]misonidazole or [14C]bromomisonidazole showed silver grains preferentially located over viable hypoxic cells in the inner half of the spheroid rim adjacent to the necrotic center, with lower grain density over nonviable necrotic areas and many fewer grains over oxic cells at the periphery of the spheroid. The results indicate that both severely and moderately hypoxic cells may preferentially bind [14C]bromomisonidazole. The data support the potential of radiolabeled bromomisonidazole for in vivo imaging pending additional studies of the metabolism of this agent.

Original languageEnglish (US)
Pages (from-to)76-85
Number of pages10
JournalRadiation Research
Volume102
Issue number1
DOIs
StatePublished - 1985
Externally publishedYes

Fingerprint

Misonidazole
spheroids
detectors
bromination
dioxane
Scintillation Counting
Halogenation
autoradiography
cells
Silver
silver
concentrates
image analysis
uptake mechanisms
drugs
metabolism
liquids
rims
Pharmaceutical Preparations
scintillation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Rasey, J. S., Krohn, K., Grunbaum, Z., Conroy, P. J., Bauer, K., & Sutherland, R. M. (1985). Further characterization of 4-bromomisonidazole as a potential detector of hypoxic cells. Radiation Research, 102(1), 76-85. https://doi.org/10.2307/3576431

Further characterization of 4-bromomisonidazole as a potential detector of hypoxic cells. / Rasey, J. S.; Krohn, Kenneth; Grunbaum, Z.; Conroy, P. J.; Bauer, K.; Sutherland, R. M.

In: Radiation Research, Vol. 102, No. 1, 1985, p. 76-85.

Research output: Contribution to journalArticle

Rasey, JS, Krohn, K, Grunbaum, Z, Conroy, PJ, Bauer, K & Sutherland, RM 1985, 'Further characterization of 4-bromomisonidazole as a potential detector of hypoxic cells', Radiation Research, vol. 102, no. 1, pp. 76-85. https://doi.org/10.2307/3576431
Rasey, J. S. ; Krohn, Kenneth ; Grunbaum, Z. ; Conroy, P. J. ; Bauer, K. ; Sutherland, R. M. / Further characterization of 4-bromomisonidazole as a potential detector of hypoxic cells. In: Radiation Research. 1985 ; Vol. 102, No. 1. pp. 76-85.
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