The OxyLite: a fibre-optic oxygen sensor.

Abstract

Tumour oxygenation is a critical determinant of success in radiotherapy and, indeed, it can be important in other forms of cancer therapy. Many attempts, extending over several decades, have been made to improve tumour oxygenation for therapeutic advantage, but no method has become established in routine clinical practice. A device for rapidly determining the local pO2 in tumours would clearly be very useful for research into these questions and perhaps also for assessment of radiobiological hypoxia in the clinic. A method that permitted continuous monitoring would be particularly valuable. Over the past decade, oxygen electrode measurements of tumour pO2 have been performed routinely in many specialized centres using the Eppendorf pO2 electrode, a thin electrode (12 or 17 mm) contained within a 300 mm diameter bevelled steel needle [1]. This form of histography has a number of disadvantages. The principal disadvantage is the electrode consumes oxygen by electrochemical reduction, causing a continuous signal decrease with time. This can result in underestimation of the pO2 level. Measurements are therefore made while driving the probe through the tumour in a stepwise manner (termed pilgrim-like, as the electrode takes ``two steps forward and one step back''), resulting in pO2 values from each stopping point in the electrode track through the tumour. A consequence of the need to keep advancing the electrode is that one cannot monitor timedependent changes in pO2 from a single location. Even if the electrode is removed and reinserted between readings, repetitive pO2 measurements from the same location may be erroneous, owing to bleeding, oedema and alteration of microcirculation in injured tissues. A more subtle problem is that the absolute reading depends on the O2 diffusion properties and oxygen solubility of the quite large volume (about 50±500 cells, see below) surrounding the electrode tip. Tumours are usually heterogeneous, and only a few viable hypoxic cells within them may be resistant to radiation. One needs to make many electrode measurements to get an idea of radiobiological hypoxia, so the large number of readings generated from each electrode track is very useful. The percentage of pO2 measurements below some threshold value determined from a frequency histogram, usually 2.5 mm Hg, is typically used to indicate the radiobiological hypoxic fraction [2]. A histogram from oxygen electrode studies of a non-Hodgkin's lymphoma and a colon carcinoma is shown in Figure 1, with the radiobiologically hypoxic fractions indicated as 63.6% and 67.7%, respectively. The second major problem lies in accurately detecting the very small electrical currents associated with low oxygen concentrations, which makes the most radiobiologically interesting regions the hardest to detect. Despite these limitations, Eppendorf electrode measurements of microregional tumour oxygenation have provided critical information about key issues in tumour hypoxia, namely: (i) most tumours have pO2 levels lower than their tissue of origin [3, 4]; (ii) direct evidence that hypoxia contributes to radioresistance [5, 6]; and (iii) tumour hypoxia is associated with malignant progression [7, 8].