Abstract
Based on both direct and indirect studies, tumor oxygenation has been shown to play an important role in clinical radiotherapeutic response. With this in mind, numerous strategies have been devised to minimize or eliminate regions of tumor hypoxia, or low oxygenation. These have included both methods for increasing oxygen delivery to the tumor7 and techniques for directly targeting the hypoxic cells using radiosensitizers or hypoxic cell cytotoxic agents.1 When combining such agents with radiotherapy, it is important to appreciate the effects of the irradiation itself on both tumor blood flow and oxygen distribution. The current study presents a method for combining several sophisticated techniques to obtain a comprehensive two-dimensional mapping of the relationships among tumor vascular configuration, oxygen transport, and hypoxic development following local tumor irradiation. First, tumor oxygen availability is spatially defined by measuring intravascular blood oxygen saturations (HbO2) cryospectrophotometrically in a frozen tumor block. Second, hypoxia development, in relation to the intravascular oxygen availability, is quantified in adjacent histological sections, using immunohistochemical detection of a nitroheterocyclic hypoxia marker (EF5). Third, a combination of fluorescent (DiOC7(3)) and immunohistological (PECAM-1/CD31) stains is used to define the distribution of distances between the tumor cells and the nearest anatomical or perfused blood vessel.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Brown JM and Giaccia AJ, Tumour hypoxia: the picture has changed in the 1990s. [Review]. Int J Radiat Biol 65:95–102, 1994.
Fenton BM, Effects of carbogen plus fractionated irradiation on KHT tumor oxygenation. Radiother Oncol 1997[in press].
Fenton BM and Gayeski TEJ, Determination of microvascular oxyhemoglobin saturations using cryospec-trophotometry. Am J Physiol 259:H1912–H1920, 1990.
Fenton BM, Paoni SF, Lee J, Koch CJ, and Lord EM, Quantification of tumor vascular development and hypoxia by combined immunohistochemical staining and intravascular HbO2 saturation measurements. Br J Cancer 1997 [in press].
Fenton BM and Way BW, Vascular morphometry of KHT and RIF-1 murine sarcomas. Radiother Oncol 28:57–62, 1993.
Hilmas DE and Gillette EL, Microvasculature of C3H/Bi mouse mammary tumors after X-irradiation. Radiat Res 61:128–143, 1975.
Horsman MR, Nordsmark M, Khalil AA, Hill SA, Chaplin DJ, et al, Reducing acute and chronic hypoxia in tumours by combining nicotinamide with carbogen breathing. Acta Oncologica — Madrid 33:371–376, 1994.
Kayar SR, Archer PG, Lechner AJ, and Banchero N, The closest-individual method in the analysis of the distribution of capillaries. Microvasc Res 24:326–341, 1982.
Lord EM, Harwell L, and Koch CJ, Detection of hypoxic cells by monoclonal antibody recognizing 2-ni-troimidazole adducts. Cancer Res 53:5721–5726, 1993.
Olive PL, Radiation-induced reoxygenation in the SCCVII murine tumour: evidence for a decrease in oxygen consumption and an increase in tumour perfusion. Radiotherapy and Oncology 32:37–46, 1994.
Song CW and Levitt SH, Vascular changes in Walker 256 carcinoma of rats following X irradiation. Radiol 100:397–407, 1971.
Thomlinson RH, Changes of oxygenation in tumours in relation to irradiation. Fron Radiat Ther Onc 3:109–121,1968.
Ting LL, Belfi CA, Tefft M, and Ngo FQH, KHT Sarcoma Blood Perfusion Change After Single-Dose X-Ray Irradiation. Int J Radiat Biol 60:335–339, 1991.
Trotter MJ, Chaplin DJ, and Olive PL, Use of a carbocyanine dye as a marker of functional vasculature in murine tumours. Br J Cancer 59:706–709, 1989.
Vaupel PW, Oxygenation of solid tumors, in: “Drug Resistance in Oncology”, Teicher BA., ed., Marcel Dekker, Inc.,New York, 1993.
Vecchi A, Garlanda C, Lampugnani MG, Resnati M, Matteucci C, et al, Monoclonal antibodies specific for endothelial cells of mouse blood vessels. Their application in the identification of adult and embryonic endothelium. Eur J Cell Biol 63:247–254, 1994.
Znati CA, Rosenstein M, Boucher Y, Epperly MW, Bloomer WD, et al, Effect of radiation on interstitial fluid pressure and oxygenation in a human tumor xenograft. Cancer Res 56:964–968, 1996.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Fenton, B.M., Paoni, S.F., Koch, C.J., Lord, E.M. (1998). Effect of Local Irradiation on Tumor Oxygenation, Perfused Vessel Density, and Development of Hypoxia. In: Hudetz, A.G., Bruley, D.F. (eds) Oxygen Transport to Tissue XX. Advances in Experimental Medicine and Biology, vol 454. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4863-8_73
Download citation
DOI: https://doi.org/10.1007/978-1-4615-4863-8_73
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7206-6
Online ISBN: 978-1-4615-4863-8
eBook Packages: Springer Book Archive