Radiosensitization with normobaric oxygen and carbogen

摘要: Although hypoxia is a cause of failure in clinical radiotherapy, the outcome trials with chemical radiosensitizers, such as misonidazole, has been disappointing [7,8]. Doselimiting toxicity restricts drug dose per fraction, so that intratumour concentrations achieved are far lower than those required for detecting radiosensitizing effect [3]. Therefore, there need to identify hypoxic cell radiosensitizers which non-toxic and effective fractionated radiotherapy. Recent studies done low radiation doses fraction clinically relevant fractionation regimes have shown, mouse mammary carcinoma, normobaric 100% oxygen an sensitizer [34]. Enhancement ratios (ER) * 1.45 1.3 (at TCDs0 level, i.e. locally control 50% tumours) were obtained 30 given overall time 6 weeks or 36 fractions 12 days (Fig. 1). These relatively small enhancement can be translated into considerable practical gain e.g. by increasing concentration from 21 100%, tumour was increased 0 80% 1 panel c). A similar could human tumours where limits response treatment. Very recently, Gatenby et al. [12] shown remarkable significant correlation between degree radiotherapy metastases head neck region levels oxygenation within these tumours. Previous whole variety rodent tumours, albeit fewer fractions, also increases radiosensitivity either carbogen (a mixture 95% 02 + 5% CO2) [10,15,18,21,32,33,37,40]. Table I Fig. 2 summarize ERs several investigators using treatments. Provided adequate pre-irradiation breathing (PIBT) used, general lie 1.6 oxygen. The sensitization gases therefore much greater seen almost all animal xenografts, radiosensitizer misonidazole [6,16,26,31]. Normobaric enhance partial pressure (pO2) intracapillary saturation haemoglobin significantly enhanced rat administration pure under normoor hyperbaric conditions [28]. Improved results amount dissolved raising systemic blood [4,25]. Furthermore, enhances flow shifts dissociation curve right, thus depressing affinity [25]. Consequently, should more Using fluorescent immunologically labelled 2-nitroimidazole stain cells, recently developed our laboratory Hodgkiss collaborators [17], decreased proportion cells CaNT extent Hypoxic 19.0 _ 1.6, 9.4 _+ 2.7 2.9 1.5% determined air, carbogen, respectively [33]. agreement slightly higher this same model, local regrowth delay assay 2, b reference 33). However, Ps0 values (i.e. at saturated oxygen) compared humans [13]