Influence of acute hypoxia and radiation quality on cell survival

Abstract

To measure the effect of acute oxygen depletion on cell survival for different types of radiation, experiments have been performed using Chinese hamster ovary (CHO) cells and RAT-1 rat prostate cancer cells. A special chamber has been developed to perform irradiations under different levels of oxygenation. The oxygen concentrations used were normoxia (air), hypoxia (94.5% N2, 5% CO2, 0.5% O2) and anoxia (95% N2, 5% CO2). Cells were exposed to X-rays and to C-, N- or O-ions with linear energy transfer (LET) values ranging from 100–160 keV/µm. The oxygen enhancement ratio (OER) and relative biological effectiveness (RBE) values have been calculated from the measured clonogenic survival curves. For both cell lines, the X-ray OER depended on the survival level. For particle irradiation, OER was not dependent on the survival level but decreased with increasing LET. The RBE of CHO cells under oxic conditions reached a plateau for LET values above 100 keV/µm, while it was still increasing under anoxia. In conclusion, the results demonstrated that our chamber could be used to measure radiosensitivity under intermediate hypoxia. Measurements suggest that ions heavier than carbon could be of additional advantage in the irradiation, especially of radioresistant hypoxic tumor regions.

223Ra and other bone-targeting radiopharmaceuticals—the translation of radiation biology into clinical practice

“…20 In clonogenic experiments, this effect can be expressed as the OER, that is, the ratio of dose required to kill a given fraction of cells in hypoxic vs oxic conditions. Various investigators have demonstrated that OER decreases with increasing LET, with Barensden 9 finding that OER reached 1 with LET of 165 keV mm 21 . 21 Thus, cells within relatively hypoxic and therefore radioresistant areas of tumour are likely to be more effectively killed by radiation of LET .100 keV mm 21 .…”

“…Various investigators have demonstrated that OER decreases with increasing LET, with Barensden 9 finding that OER reached 1 with LET of 165 keV mm 21 . 21 Thus, cells within relatively hypoxic and therefore radioresistant areas of tumour are likely to be more effectively killed by radiation of LET .100 keV mm 21 .…”

“…One of these was a single-dose dose-response trial involving 100 patients; each given a single infusion of 223 Ra at one of four dose levels (5, 25, 50 or 100 kBq kg 21 ). This found a dose-dependent improvement in pain and further found 223 Ra to be well tolerated at all dose levels up to the maximum of 100 kBq kg 21 .…”

“…One of these was a single-dose dose-response trial involving 100 patients; each given a single infusion of 223 Ra at one of four dose levels (5, 25, 50 or 100 kBq kg 21 ). This found a dose-dependent improvement in pain and further found 223 Ra to be well tolerated at all dose levels up to the maximum of 100 kBq kg 21 . The commonest toxicities were haematological and gastrointestinal with 43%, 24% and 22% experiencing nausea, vomiting and diarrhoea, respectively, whilst grade 3-4 anaemia, leucopenia, neutropenia and thrombocytopaenia were seen in 8%, 1%, 3% and 6% of patients treated, respectively.…”

Radium-223: Insight and Perspectives in Bone-metastatic Castration-resistant Prostate Cancer

“…Alpha particles are considered more cytotoxic than beta particles, especially under hypoxic conditions (23,24) and, because of their higher biological efficacy, the required activity is lower than that of beta particles.…”