Disease relevance of NSC318502

• EXPERIMENTAL DESIGN: Twenty-one patients received an i.v. infusion of the hypoxia marker pimonidazole hydrochloride before multiple tumor biopsies [1].
• EXPERIMENTAL DESIGN: Thirty-four patients with squamous cell carcinoma of the uterine cervix were infused with pimonidazole hydrochloride solution [2].
• The hypoxic cell radiosensitizers Ro 03-8799 and SR 2508 have different clinical toxicities [3].
• Effects of localised tumour hyperthermia on pimonidazole (Ro 03-8799) pharmacokinetics in mice [4].
• Both compounds were concentrated in all the tumors, the concentration increases or decreases as a function of the time, depending on the cell line; there was more Ro 03-8799 in the pigmented melanomas than in the other tumors [5].

High impact information on NSC318502

• METHODS: Mice (MF1) bearing LS174T human tumor xenografts were injected with premixed (18)F-FDG (100 MBq), (14)C-2DG (0.37 MBq), and pimonidazole hydrochloride (60 mg/kg) [6].
• METHODS AND MATERIALS: Eighteen patients diagnosed with squamous cell carcinoma of the uterine cervix or head and neck were infused intravenously with a solution of pimonidazole hydrochloride at a dose of 0.5 gm/m2 [7].
• Pimonidazole hydrochloride and an IgG1 mouse monoclonal antibody were used to detect hypoxia, and a mouse antimetallothionein monoclonal antibody (DAKO) was used to detect Type I and II metallothionein in sets of contiguous tissue sections [8].
• SR-2508 produces peripheral neuropathy, whereas Ro 03-8799 causes acute CNS toxicity [9].
• Using clinically relevant doses, mean Sensitizing Enhancement Ratio (SER) values for HRT18 were: 1.3 (Ro 03-8799: 0.1 mg/gram body weight (gbw) or SR-2508: 0.2 mg/gbw), and 1.5 (Ro 03-8799: 0.1 mg/gbw + SR-2508: 0.2 mg/gbw) [9].

Chemical compound and disease context of NSC318502

• The effects of whole body hyperthermia on the pharmacokinetics and toxicity of the basic 2-nitroimidazole radiosensitizer Ro 03-8799 in mice [10].
• The main purpose of this study was to investigate whether previously shown teratogenic doses on GD 11 and 13 of the selective IKr blocker almokalant (ALM) induce hypoxia in rat embryos in vivo by using the hypoxia marker pimonidazole hydrochloride (PIM) [11].
• In short, based on cellular toxicity data, Ro 03-8799 appears to offer no advantage over misonidazole as a selective cytocidal agent for hypoxic cells, but RSU-1164 does provide a moderate therapeutic advantage [12].

Biological context of NSC318502

• Pharmacokinetics of Ro 03-8799 in mice bearing melanosarcoma: comparison with tumors without melanin [13].
• From bivariate analysis, cumulative AUC for Ro 03-8799 has the most significant correlation with the development of peripheral neuropathy [3].
• WBH markedly reduced Ro 03-8799 LD50/7d from 779 to 259 micrograms g-1 (P less than 0.001) [10].
• These observations added to the reports concerning toxicology in monkeys and rats and radiosensitizing efficiency in the laboratory, suggest that Ro 03-8799 may prove to be much more effective sensitizer than misonidazole in man [14].
• Glucose and lipid metabolism in the brain, liver and in a transplanted tumour were found to be variously altered within 2 to 3 h of administering single doses of the radiosensitizer Ro-03-8799 to normal and tumour-bearing mice [15].

Anatomical context of NSC318502

• The hypoxic cell radiosensitizer Ro 03-8799 produces acute central nervous system toxicity which limits repeated doses of the drug to 0.75 g/m2, but peripheral neuropathy does not occur [16].
• The pharmacokinetics of Ro 03-8799 and SR-2508 were studied in 6 tumor cell lines (5 human, 1 murine) transplanted into athymic nude mice [5].
• Morphological changes in rat hepatocytes in primary culture induced by Misonidazole, desmethylmisonidazole and Ro 03-8799 [17].

Associations of NSC318502 with other chemical compounds

• Plasma pharmacokinetics for Ro 03-8799 were similar to previous experience, but for SR 2508 the terminal half-life was greater in this series by a factor of 1 [18].
• WBH greatly inhibited glomerular filtration (51Cr EDTA clearance) during heating, contributing to the increased plasma Ro 03-8799 concentrations [10].
• WBH increased peak plasma concentrations of the Ro 03-8799 N-oxide metabolite Ro 31-0313 by 61% and the beta-phase AUC of i.v. administered Ro 31-0313 by 36% [10].
• Two hypoxic cell radiosensitizers, RSU-1069 and Ro-03-8799 were investigated for their in vitro cytotoxicity and ability to induce oncogenic transformation and sister chromatid exchanges in the C3H 10T1/2 cell system [19].
• A comparative study of Ro 03-8799: racemic mixture and enantiomers [20].

Analytical, diagnostic and therapeutic context of NSC318502

• The hypoxic cell sensitizer Ro 03-8799 has been given with radiotherapy to achieve complete and sustained regression in 5 of 7 cases of recurrent malignant melanoma treated with the object of cure and in 1 of 3 treated palliatively [21].
• A new hypoxic cell radiosensitiser, Ro 03-8799 has been administered intravenously to human volunteers and its kinetic parameters derived from plasma and urine data [22].
• Vascular parameters and oxygenation status of the xenografts were determined immunohistochemically in frozen sections of the tumors, using the hypoxia marker pimonidazole-hydrochloride to detect hypoxic areas [23].

References