Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

• Published in: British journal of cancer Vol. 100; no. 4; pp. 644 - 648
• Main Authors: Alonzi, R, Padhani, A R, Maxwell, R J, Taylor, N J, Stirling, J J, Wilson, J I, d′Arcy, J A, Collins, D J, Saunders, M I, Hoskin, P J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.02.2009; Nature Publishing Group
• Subjects: Aged; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carbon Dioxide - blood; Carbon Dioxide - metabolism; Cell Hypoxia; Cell Line, Tumor; Drug Resistance; Epidemiology; Human subjects; Humans; Hypoxia; Magnetic Resonance Imaging; Male; Medical prognosis; Medical research; Medical sciences; Mice; Middle Aged; Molecular Medicine; Neoplasm Transplantation - diagnostic imaging; Nephrology. Urinary tract diseases; Oncology; Oxygen - blood; Oxygen - metabolism; Oxygen Inhalation Therapy; Prostate cancer; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - therapy; Radiation therapy; Radiography; Translational Therapeutics; Transplantation, Heterologous; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; United Kingdom > UK; hypoxia; prostate cancer; magnetic resonance imaging; BOLD; carbogen; Prostate disease; Transplantation; Heterotransplantation; Cancerology; Surgery; Graft; Male genital diseases; Human; Oxygen; Urinary system disease; Rodentia; Malignant tumor; Nuclear magnetic resonance imaging; Genetic translation; Vertebrata; Mammalia; Treatment; Mouse; Animal; Medical imagery; Hypoxia; Oxygenation; Prostate cancer; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604903

Hypoxia has been associated with poor local tumour control and relapse in many cancer sites, including carcinoma of the prostate. This translational study tests whether breathing carbogen gas improves the oxygenation of human prostate carcinoma xenografts in mice and in human patients with prostate cancer. A total of 23 DU145 tumour-bearing mice, 17 PC3 tumour-bearing mice and 17 human patients with prostate cancer were investigated. Intrinsic susceptibility-weighted MRI was performed before and during a period of carbogen gas breathing. Quantitative R 2 * pixel maps were produced for each tumour and at each time point and changes in R 2 * induced by carbogen were determined. There was a mean reduction in R 2 * of 6.4% ( P =0.003) for DU145 xenografts and 5.8% ( P =0.007) for PC3 xenografts. In all, 14 human subjects were evaluable; 64% had reductions in tumour R 2 * during carbogen inhalation with a mean reduction of 21.6% ( P =0.0005). Decreases in prostate tumour R 2 * in both animal models and human patients as a result of carbogen inhalation suggests the presence of significant hypoxia. The finding that carbogen gas breathing improves prostate tumour oxygenation provides a rationale for testing the radiosensitising effects of combining carbogen gas breathing with radiotherapy in prostate cancer patients.