TY - JOUR
T1 - Microelectrode measurements of photochemical oxygen depletion in multicell tumor spheroids during photodynamic therapy
AU - Nichols, Michael G.
AU - Foster, Thomas H.
N1 - Funding Information:
The work reported here has been supported by USPHS grant CA36856 and by a grant from the American Lung Association of NY State. M.G.N. gratefully acknowledges a grant-in-aid of research from Sigma Xi. The authors wish to thank Donna Hartley for technical assistance, Shari Harwell for preparation of Figure 1 , and Russell Hilf and Scott Gibson for helpful discussions on many aspects of photodynamic therapy. Finally, we thank Mr. Stewart Levine of the Diamond General Development Corp. for his expertise and patience in guiding us through the mysterious world of oxygen-sensitive microelectrodes.
Publisher Copyright:
© 1994 SPIE. All rights reserved.
PY - 1994/7/19
Y1 - 1994/7/19
N2 - We have previously reported results of experiments in which EMT6/Ro spheroids were subjected to Photofrin®-PDT consisting of a fixed incident fluence (60 J-cm-2) delivered at 200, 50, and 25 mW-cm-2. Surviving fractions from treated spheroids decreased as the incident fluence rate was lowered over this range. We have interpreted these data using a model wherein the cells comprising the surviving fractions are assumed to originate from within a therapy-induced anoxic volume resulting from Type-il photochemistry. In this paper, we demonstrate direct measurements of the phenomenon in individual photosensitized EMT6 spheroids. Steadystate measurements of 3O2 gradients in and around metabolizing spheroids allow determination of the 3O2 diffusion constant and the rate of metabolic 3O2 consumption within a spheroid. Timedependent measurements obtained at a single spatial location during laser irradiation are fit to numerical solutions of a pair of time-dependent diffusion with consumption equations. Fits allow a determination of the rate of PDT-induced 3O2 consumption. Based on these fits, it is possible to calculate the spatial and temporal distributions of oxygen within a spheroid undergoing PDT.
AB - We have previously reported results of experiments in which EMT6/Ro spheroids were subjected to Photofrin®-PDT consisting of a fixed incident fluence (60 J-cm-2) delivered at 200, 50, and 25 mW-cm-2. Surviving fractions from treated spheroids decreased as the incident fluence rate was lowered over this range. We have interpreted these data using a model wherein the cells comprising the surviving fractions are assumed to originate from within a therapy-induced anoxic volume resulting from Type-il photochemistry. In this paper, we demonstrate direct measurements of the phenomenon in individual photosensitized EMT6 spheroids. Steadystate measurements of 3O2 gradients in and around metabolizing spheroids allow determination of the 3O2 diffusion constant and the rate of metabolic 3O2 consumption within a spheroid. Timedependent measurements obtained at a single spatial location during laser irradiation are fit to numerical solutions of a pair of time-dependent diffusion with consumption equations. Fits allow a determination of the rate of PDT-induced 3O2 consumption. Based on these fits, it is possible to calculate the spatial and temporal distributions of oxygen within a spheroid undergoing PDT.
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U2 - 10.1117/12.179983
DO - 10.1117/12.179983
M3 - Conference article
AN - SCOPUS:84979729914
VL - 2133
SP - 260
EP - 271
JO - Proceedings of SPIE - The International Society for Optical Engineering
JF - Proceedings of SPIE - The International Society for Optical Engineering
SN - 0277-786X
T2 - Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy III 1994
Y2 - 23 January 1994 through 29 January 1994
ER -