Reoxygenation Rate Research Articles

The potential benefit from a perfect radiosensitizer and its dependence on reoxygenation.

The potential benefit of a perfect radiosensitizer has been assessed by computing the sensitization ratios that would be observed in a mixed population of oxic and hypoxic cells if different reoxygenation rates existed. The sensitizer has been assumed to be as effective as oxygen, completely non-toxic and freely diffusible to all hypoxic cells within the tumour. The calculations have been made for several different clinical fractionation regimes, namely 30, 20, 9 or 6 fractions, all with the same ret dose (NSD = 1700 rets). These calculations have allowed us to deduce how large the observed sensitization would be for differing rates of reoxygenation and for the different fractionation schemes. The size of the extrapolation number is seen to be an important parameter in these calculations. They have allowed us to indicate how much reoxygenation would be needed to abolish the benefit from (and hence the need for) a perfect radiosensitizer.

Misonidazole in fractionated radiotherapy: are many small fractions best?

Computer simulations have been made of four radiotherapy fractionation regimes either in current use or proposed for clinical trials of misonidazole. A variety of cell-survival parameters and reoxygenation patterns have been used. The models allow the relative importance of repair capacity, reoxygenation rate, and dose per fraction to be assessed for these four schedules in the presence or absence of misonidazole. Unlike hyperbaric oxygen, the dose of misonidazole and the fractionation scheme to be used are critically interdependent, because the total drug dose is limited to 12 g/m2 by its neurotoxicity, regardless of the extent to which it is fractionated. The largest sensitizing effect is always demonstrated with six fractions, each given with 2 g/m2 of misonidazole. In the absence of reoxygenation a sensitizer enhancement ratio of 1.7 is predicted, but this falls to 1.1--1.2 if extensive reoxy-generation occurs. Less sensitization is observed with 30 fractions, each with 0.4 g/m2 of drug. However, for clinical use, the important question is which treatment kills the maximum number of tumour cells. Many of the simulations predict a marked disadvantage of reducing the fraction number for X rays alone. The circumstances in which this disadvantage is offset by the large SER values with a six-fraction schedule are few. The model calculations suggest that many small fractions, each with a low drug dose, are safest unless the clinician has some prior knowledge that a change in fraction number is not disadvantageous.

A Method for Precalibrating Re-oxygenation Rates in Experimental Containers

Abstract A precalibration procedure is outlined that ensures sufficient re-oxygenation to balance oxygen demand in static containers used to hold small aquatic animals for experiment or observation. The procedure is based on predicting the rate of controlled turbulence at which re-oxygenation balances oxygen consumption at some acceptable oxygen concentration below saturation.

The Response of Viable Tumor Cords to a Single Dose of Radiation

A C3H mouse mammary tumor contained cords of viable tissue separating vascular and connective stroma from regions of necrosis. The mean distance from capillary to necrotic tissue was about 90 ,um, a value close to the calculated diffusion distance for oxygen. Doses of 600 and 2000 rads y-radiation to the tumor caused increasing delays in tumor growth but no significant reduction in volume; 3000 rads given under conditions of acute local hypoxia caused slight tumor regression followed by slow regrowth. After each of these doses the mean thickness of tumor cords shrank rapidly to about 50% of the control value at about 12 hr after irradiation, and then started to increase. The mean concentration of cells within the tumor cords also decreased after irradiation. Thus, changes in tumor volume were not representative of microscopic changes in cell number. The rate of recovery of cord thickness was dose dependent, and after 2000 rads or 3000 rads hypoxic cords regrew to a mean thickness less than that in unirradiated tumors. Changes in tumor oxygenation with time after irradiation are dependent on these changes in microarchitecture and are compared with rates of reoxygenation that have been estimated by other methods.

Cell kinetic model of tumour growth and regression for a rhabdomyosarcoma in the rat: Undisturbed growth and radiation response to large single doses

A mathematical model of tumour growth and regression has been developed using experimental data on the cellular kinetics and radiation survival of cells of a rhabdomyosarcoma in the WAG/Rij rat. For the undisturbed tumour, the model assumes a time-dependent mean cell cycle time, cell proliferation parameter ( 1 + growth fraction) and cell-loss rate, consistent with available experimental data, to predict the (non-exponential) time variation of the tumour volume. To treat the response to radiation, it is assumed that the irradiated tumour is composed of two components: the “doomed” population, those cells which are incapable of unlimited proliferation but may undergo several divisions before dying, and the “surviving” population, those cells which may have received non-lethal damage but are capable of unlimited proliferation. Time dependence of the proliferating fraction, the cell density, and the reoxygenation rate are introduced to describe the regression and regrowth of the tumour after single massive radiation doses. The results show that reasonable time dependences of the parameters describe the response of the tumour to 2000 and 1000 rads of X-rays. A long delay in tumour regrowth after 600 rads of fast neutrons, however, remains to be adequately explained in terms of the model in its present form.

The influence of intracellular recovery and hypoxic cells on the radiation response of mammary tumours and skin in C3H mice.

Spontaneous and transplanted tumours in the C3H mouse have been irradiated in oxygen at one atmosphere absolute using either single doses or doses split into two equal fractions with the time interval between them being varied from one hour to three days. The response of the tumours was compared with that of the skin over and around the tumour as representing normal tissue. Intracellular recovery for both tumour types, shown by a positive (D2–D1) 6 hours was seen at all doses studied, and evidence was given for recovery in the hypoxic proportion of the tumour. The skin showed a gradual decrease in (D2–D1) 6 hours as the dose increased, until after an initial dose of 2,750 rads no intracellular recovery was seen with a negative (D2–D1) at all intervals up to three days. This and the sensitisation in the tumours seen at longer time intervals (i.e. negative (D2–D1)) are interpreted as reoxygenation phenomena, or change in proportion of hypoxic cells. The rate and amount of reoxygenation were observed to be greater in spontaneous than in transplanted tumours. The therapeutic advantages of short time intervals are discussed.

Field Techniques for Evaluating Aerators

Rational design and operation of an aerated biological unit requires a knowledge of the oxygen-transfer capacity of the aeration systems either under consideration or installed. Detailed methods are described for use by operating engineers in collecting the required performance data through tests of commercial aerators installed in full-scale basins. The essential features of oxygen-transfer theory are reviewed together with the relationships needed to adjust the test data to specified conditions. The important test conditions, the required auxiliary measurements, and the basic oxygen-transfer measurements are enumerated. The results of full-scale tests based on reoxygenation rates, gas-stream oxygen balances, sulfite-ion depletion rates, and biological oxygen-uptake rates are presented for large sparged turbine and entrainment aerators. The ASCE Committee on Sanitary Engineering Research is considering means of collecting, correlating, and publishing the results obtained by plant engineers and their consultants in using these techniques to conduct aerator tests.