title: Measurements of tumor tissue oxygen tension using a time-resolved luminescence-based optical oxylite probe: comparison with a paired survival assay.
abstract: Recently, a system that measures tissue oxygen tension using time-resolved luminescence-based optical sensors has become available commercially (Oxford Optronix, Oxford, England). Two experiments were conducted using this system. First, the oxygen tension distribution was measured in two tumor lines: a spontaneous mouse fibrosarcoma, FSa-II, and a human squamous cell carcinoma xenograft, FaDu. The area in which the pO(2) was equal to or lower than 2.5 mmHg was defined as the hypoxic lesion, and the hypoxic cell fraction was taken as the fraction of these measurements in a tumor. The measured hypoxic cell fractions were compared with those determined by the paired cell survival assay for tumors of various sizes. Second, the tumor tissue pO(2) was measured continuously after administration of two different anesthetics to evaluate the effect of these drugs on tissue pO(2). Results indicated a good agreement between the hypoxic cell fractions measured by this system and those determined by the paired cell survival curve assay for tumors smaller than approximately 500 mm(3). For tumors larger than approximately 500 mm(3), the hypoxic cell fractions measured by the oxygen probe system were higher than those measured by the paired cell survival assay. This may suggest that the hypoxic cell fraction measured by the oxygen probes included both hypoxic and necrotic areas in large tumors where necrotic lesions occupied a significant portion of the tumor. Continuous measurements of pO(2) after anesthesia (Nembutal, or ketamine plus xylazine) showed a consistent rise in the pO(2) during the first 20-30 min of measurement. Subsequently, the pO(2) values became constant or continued to rise slowly. For comparison, the tumor cell survivals were assayed after a dose of 20 Gy given in air at 5, 20 and 60 min after anesthesia. The result showed a decrease in cell survival only in tumors irradiated 20 min after an injection of Nembutal.
authors.affiliation: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. ysurano@aol.com
authors.forename: Muneyasu
authors.initials: M
authors.lastname: Urano
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Humm
authors.forename: Jason A
authors.initials: JA
authors.lastname: Koutcher
authors.forename: Pat
authors.initials: P
authors.lastname: Zanzonico
authors.forename: Clifton
authors.initials: C
authors.lastname: Ling
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005354:Fibrosarcoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007649:Ketamine / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D010100:Oxygen / Q000032:analysis*; D010313:Partial Pressure; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D007649:Ketamine; D010100:Oxygen