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Hypoxia in Du-145 Prostate Cancer Xenografts After Estramustine Phosphate and Radiotherapy

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Purpose: Practically all solid malignant tumours have central hypoxia, which makes them less vulnerable to most forms of both radiotherapy and chemotherapy. Estramustine phosphate (EMP) is known to sensitise cancer cells and tumours to irradiation and to increase blood flow in malignant tumours. This study was designed to assess the effect of EMP and radiotherapy on the oxygenation status of the tumours.

Methods and Materials: Nude mice with DU 145 human prostate cancer cell tumours were divided into four groups: group ER was treated with EMP 0.2 mg/d and external irradiation 3 × 6 Gy; group E received EMP, group R irradiation only; and group O no treatment. The degree of hypoxia in the tumours before and after treatment was measured using 18F-labelled fluoromisonidazole ([18F]FMISO) as a marker. The testis served as a control organ. Histological samples were studied for necrosis and proliferation (DAPI-stain for mitoses and Ki-67).

Results: The tumours showed more [18F]FMISO uptake, indicating more hypoxia, than the testes in all four groups. EMP did not improve tumour oxygenation but enhanced the ability of radiotherapy to cause tumour necrosis.

Conclusions: The angiogenic effect of EMP, if present, is not crucial in the mechanism of radiosensitation.
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Keywords: BT4C; DAPI-stain for mitoses and Ki-67; DNA; DU-145; Dunnett's method; Dunning R 3327; Estramustine; Estramustine Phosphate; G2/M-phase; Immunohistochemistry; Monoclonal antibody PP-67; Nitroimidazoles; Prostate Cancer Xenografts; R3327; Rat glioma model; SAS/STAT® software; analysis of variance (ANOVA); angiogenesis; carcinomas; central hypoxia; central necrosis; chemotherapy; deoxyribonucleic acid; fluorescein isothiocyanate (FITC)-coupled goat; fluorine-18 labelled fluoromisonidazole; fluoromisonidazole; hormone-independent prostate cancer; human prostate cancer; hypoxia; hypoxia-specific factor; malignant tumours; necrosis; neovascularisation; neurological malignancies; polymethylmethacrylate; positron emission tomography (PET) technology; prostate carcinoma model; radiosensitation; radiotherapy; tumour necrosis; vascular endothelial growth factor

Document Type: Research Article

Publication date: October 1, 2010

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  • Current Radiopharmaceuticals publishes original research articles, letters, reviews, drug clinical trial studies and guest edited issues on all aspects of research and development of radiolabelled compound preparations. The scope of the journal covers the following areas: radio imaging techniques, therapies; preparation and application of radionuclide compounds including the incorporation of tracer methods used in scientific research and applications.
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