Oxygen Consumption and Diffusion Effects in Photodynamic Therapy

Effects of oxygen consumption in photodynamic therapy (PDT) are considered theoretically and experimentally. A mathematical model of the Type II mechanism of photooxidation is used to compute estimates of the rate of therapy-dependent in vivo oxygen depletion resulting from reactions of singlet oxyg...

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Bibliographic Details
Published in:	Radiation research Vol. 126; no. 3; pp. 296 - 303
Main Authors:	Foster, Thomas H., Murant, Richards S., Bryant, Robert G., Knox, Robert S., Gibson, Scott L., Hilf, Russell
Format:	Journal Article
Language:	English
Published:	Oak Brook, Il Academic Press, Inc 01-06-1991 Radiation Research Society
Subjects:	Animals Biological and medical sciences Diffusion Female Fundamental and applied biological sciences. Psychology General aspects Irradiation Lipids Mammary Neoplasms, Experimental - drug therapy Mammary Neoplasms, Experimental - metabolism Mammary Neoplasms, Experimental - pathology Models, Chemical Molecular and cellular biology Oxygen Oxygen consumption Oxygen Consumption - physiology Oxygen metabolism Photochemotherapy Radiotherapy Rats Rats, Inbred F344 Singlet oxygen Space life sciences Tissue oxygenation Tumors Parameter estimation Radiobiology Animal Oxygen consumption Biophysics Malignant tumor Mathematical model Radiotherapy Fractionated dose Phototherapy
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Summary:	Effects of oxygen consumption in photodynamic therapy (PDT) are considered theoretically and experimentally. A mathematical model of the Type II mechanism of photooxidation is used to compute estimates of the rate of therapy-dependent in vivo oxygen depletion resulting from reactions of singlet oxygen (1 O2) with intracellular substrate. Calculations indicate that PDT carried out at incident light intensities of $50\ {\rm mW}/{\rm cm}^{2}$ may consume 3 O2 at rates as high as $6-9\ \mu M\ {\rm s}^{-1}$. An approximate model of oxygen diffusion shows that these consumption rates are large enough to decrease the radius of oxygenated cells around an isolated capillary. Thus, during photoirradiation, cells sufficiently remote from the capillary wall may reside at oxygen tensions that are low enough to preclude or minimize ^{1}{\rm O}{}_{2}\text{-mediated}$ damage. This effect is more pronounced at higher power densities and accounts for an enhanced therapeutic response in tumors treated with $360\ {\rm J}/{\rm cm}^{2}$ delivered at $50\ {\rm mW}/{\rm cm}^{2}$ compared to the same light dose delivered at $200\ {\rm mW}/{\rm cm}^{2}$. The analysis further suggests that the oxygen depletion could be partially overcome by fractionating the light delivery. In a transplanted mammary tumor model, a regimen of 30-s exposures followed by 30-s dark periods produced significantly longer delays in tumor growth when compared to the continuous delivery of the same total fluence.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0033-7587 1938-5404
DOI:	10.2307/3577919