Comparison of radiolabeled bromomisonidazole and misonidazole as probes for hypoxic tissue

Conference · Sun Jan 01 04:00:00 EST 1984 · J. Nucl. Med.; (United States)

OSTI ID:6594127

Rasey, J S; Krohn, K A; Nelson, N; Grunbaum, Z

Misonidazole and related nitroimidazoles may be useful for diagnostic detection of hypoxic cells in tumor, stroke, or myocardial infarct due to binding by metabolic reactions which are limited to cells with low oxygen tension. 4-Bromo-misonidazole has been synthesized from misonidazole. If labeled with a gamma emitting bromine isotope, it may be useful in nuclear imaging of hypoxic tissue. It has been compared to misonidazole in radiolabeled form as a probe for hypoxic cells in an in vitro tumor model, the multi-cellular tumor spheroids. This system is useful for screening nuclear imaging agents. These ''pseudo tumors'' have cell-cell contact, three dimensional growth, and development of central necrosis similar to in vivo tumors, but lack the complications of a vascular system and host physiological influences. EMT-6 tumor cell spheroids with necrotic, hypoxic cores were incubated with 50 ..mu..m C-14-bromomisonidazole or C-14-misonidazole. Maximum levels of C-14-bromomisonidazole (approx 5 fold medium levels) were attained by 10 hrs while C-14-misonidazole uptake reached a similar maximum level only after 23 hrs. In autoradiographs, essentially no label from bromomisonidazole or misonidazole accumulated in oxic cells at the periphery of the spheroid while cells presume to be hypoxic but viable adjacent to the necrotic center were heavily labeled at incubation time greater than or equal to 5 hrs. HPLC techniques can separate C-14-misonidazole from C-14-bromomisonidazole and will allow us to determine if bromine remains attached to stably bound C-14 labeled compounds after spheroids have metabolized C-14-bromomisonidazole.

• Research Organization: Univ. of Washington, Seattle, WA 98195
• OSTI ID: 6594127
• Report Number(s): CONF-840619-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 25:5
• Country of Publication: United States
• Language: English

Related Subjects

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550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANOXIA
ANTINEOPLASTIC DRUGS
AUTORADIOGRAPHY
AZOLES
BIOCHEMISTRY
CHEMISTRY
COMPARATIVE EVALUATIONS
DISEASES
DISTRIBUTION
DRUGS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
IN VIVO
LABELLED COMPOUNDS
LABELLING
METABOLISM
MISONIDAZOLE
NECROSIS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOLOGICAL CHANGES
RADIOPHARMACEUTICALS
RADIOSENSITIZERS
TISSUE DISTRIBUTION
TUMOR CELLS