The Place of Oxygen in Radiotherapy

Churchill-Davidson, I.; Foster, Carl; Wiernik, G.; Collins, C. D.; Pizey, N. C. D.; Skeggs, D.; Purser, P. R.

doi:10.1259/0007-1285-39-461-321

Cited by 68 publications

(9 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Flow cytometric analysis of stained cells is facilitated by co-staining cellular DNA, which allows discrimination of single cells in the sample and rejection of cell clumps and debris. The alternative use of an immunoperoxidase-conjugated anti-serum has been used to demonstrate the localisation of hypoxic cells in frozen tumour sections.The existence of poorly oxygenated radioresistant cells in tumours is thought to be one of the factors contributing to local failure of radiotherapy and tumour regrowth (Gray et al, 1953;Churchill-Davidson et al, 1966;Bush et al, 1978;Mueller-Klieser et al, 1981;Dische, 1985;Dische et al, 1986;Overgaard et al, 1986). A simple, rapid clinical test for the presence of hypoxic cells in tumours could enable radiotherapy to be optimised for individual patients on the basis of the oxygen status of their tumours.…”

mentioning

confidence: 99%

Flow cytometric evaluation of hypoxic cells in solid experimental tumours using fluorescence immunodetection

Hodgkiss

Jones²,

Long³

et al. 1991

Br J Cancer

View full text Add to dashboard Cite

Summary Numerous methods have been proposed for the detection of hypoxic cells using nitroimidazoles labelled with both radioactive and stable isotopes where the isotopic label becomes bound as a result of reductive metabolism of the nitro group. A new probe for hypoxia, 7-(4'-(2-nitroimidazol-1-yl)-butyl)-theophylline, is described where an immunologically recognisable hapten (theophylline) is covalently linked to a 2-nitroimidazole. Bioreduction of the nitroimidazole leads to binding of bioreductive metabolites, and hence the theophylline side-chain, to intracellular molecules. Immunochemical procedures are then used to stain cells containing the bound theophylline using an FITC-conjugated anti-serum. Flow cytometric analysis of stained cells is facilitated by co-staining cellular DNA, which allows discrimination of single cells in the sample and rejection of cell clumps and debris. The alternative use of an immunoperoxidase-conjugated anti-serum has been used to demonstrate the localisation of hypoxic cells in frozen tumour sections.The existence of poorly oxygenated radioresistant cells in tumours is thought to be one of the factors contributing to local failure of radiotherapy and tumour regrowth (Gray et al., 1953;Churchill-Davidson et al., 1966;Bush et al., 1978;Mueller-Klieser et al., 1981;Dische, 1985;Dische et al., 1986;Overgaard et al., 1986). A simple, rapid clinical test for the presence of hypoxic cells in tumours could enable radiotherapy to be optimised for individual patients on the basis of the oxygen status of their tumours. Adjuncts to radiotherapy such as hypoxic cell sensitisers and hyperbaric or normobaric oxygen could then be administered to those patients most likely to benefit from them.Of the methods that have been proposed for determining the hypoxic fractions of tumours, several are based on the hypoxia-dependent bioreductive metabolism of a labelled 2-nitroimidazole which results in binding of labelled fragments of the original compound to cellular macromolecules. Various labels have been proposed, including 3H (Raleigh et al., 1985), 14C (Chapman et al., 1981;Franko & Chapman, 1982; Garrecht & Chapman, 1983), 75Br, 76Br, 7Br (Rasey et al., 1985 and '9F (Raleigh et al., 1986): 3H-misonidazole has been administered to small numbers of patients with treatment-resistant tumours (Urtasun et al., 1986). Identification of hypoxic cells using radiolabelling requires prolonged autoradiography to detect labelled regions of tumour sections. NMR detection of bioreductively bound metabolites of fluorinated nitroimidazoles in tissues has been demonstrated experimentally and such bound metabolites have also been detected by fluorescence immunohistochemistry (Raleigh et al., 1987).In this paper, we describe the use of the immunologically detectable hapten theophylline, covalently bound to a 2-nitroimidazole, as a method of identifying hypoxic cells. An isotopic label on the side-chain of misonidazole binds to cellular constituents as efficiently as a ring label (Raleigh et al., 1985) and an immun...

show abstract

mentioning

confidence: 99%

Flow cytometric evaluation of hypoxic cells in solid experimental tumours using fluorescence immunodetection

Hodgkiss

Jones²,

Long³

et al. 1991

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…I n view of the fact that so many patients with advanced disease die of their metastases, we may have to be satisfied with 10 to 20% improvements in survival even if the rate of local control should approach perfection. Inclusion of earlier stages may produce more significant differences.…”

Section: Trials Of Othermentioning

confidence: 99%

Hyperbaric oxygen in radiation therapy

Glassburn¹,

Brady²,

Plenk³

1977

Cancer

View full text Add to dashboard Cite

The importance of oxygen with low LET radiations has been established beyond any doubt in many different systems, both plant and animal. While some studies, especially head and neck tumors, are impressive, it has not been demonstrated unequivocally that radiation under hyperbaric conditions is superior to well fractionated, well conceived, conventional radiotherapy. Any resulting gain in survival from the addition of hyperbaric oxygen will be limited, especially with more advanced stages of disease. Well controlled studies, especially with earlier stage disease, are still necessary. It would be worthwhile to undertake such trials, especially with tumors of the head and neck constituting the most promising site of study, as others have noted, since even a 5% to 10% improvement in survival would mean many lives saved. Continued trials with hyperbaric oxygen, oxygen in other forms, neutrons and other particles, and radiation sensitizing drugs are all justified in an attempt to overcome the oxygen effect on human tumors.

show abstract

“…The hypoxia arose in many tumors because of inefficient delivery of oxygen via the poorly organized tumor vasculature [1,2,3]. It was clear that tumor hypoxia reduced the efficacy of radiotherapy and in some cases contributed to local failure of radiotherapy and tumor regrowth.…”

Section: Introductionmentioning

confidence: 99%