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Lack of Reciprocity in Drug and Light Dose Dependence of Photodynamic Therapy of Pancreatic Adenocarcinoma in Vitro¹

Great Lakes Biomedical Laser Research Center, Department of Oral and Maxillofacial Surgery, State University of New York at Buffalo, Buffalo, New York 14214-3008 [T. S. M.]; Robert-Roessle-Clinic, Robert-Roessle-Strasse 10, O-1115 Berlin-Buch, Germany [K. T. M.]; and Departments of Radiation Biology [S. O. N-F.] and Biomathematics [W. R. G., J. C. P.] and Grace Cancer Drug Center [W. R. G.], Roswell Park Cancer Institute, New York State Department of Health, Buffalo, New York 14263-0001

Two human pancreatic cell lines, MIA PaCa 2 and Capan 2, were treated by photodynamic therapy in vitro with Photophrin (0.01–25 µg/ml; 24 h) and then light (1–50 J/cm²; = 630 nm). The following model was fit to 6 datasets with weighted nonlinear regression: where F = 1 or or The symbols are: E, cell growth; Econ, control growth in the absence of the combination; B, background signal; m, slope parameter; , interaction parameter; D, concentration of Photofrin; L, light dose; F, fraction of Photofrin not photobleached by the light dose; k, k₁, k₂, bleaching parameters; A, distribution parameter for biexponential bleaching equation. Simple reciprocity of photosensitizer concentration and light dose was not found; compensation for photobleaching was critical. MIA PaCa2 required the monoexponential bleaching factor, whereas Capan 2 required the biexponential bleaching factor. The greater photosensitivity of MIA PaCa2 over Capan 2 can be best explained not by differences in the interaction parameter but rather by differences in the photobleaching pattern and rate. It may be possible to further enhance the selectivity of photodynamic therapy if differences in photobleaching between different cell types can be exploited by adequate dosimetry.

¹ Supported by National Cancer Institute Grants CA47299, CA55791, CA46732, RR10742 and CA16056. K. T. M. received support from Deutsche Forschungsgemeinschaft (Bad Godesberg, Germany).

² To whom requests for reprints should be addressed, at Department of Oral and Maxillofacial Surgery, 112 Squire Hall, State University of New York at Buffalo, 3435 Main Street, Buffalo, NY 14214-3008.

Received 8/ 2/94. Accepted 5/16/95.

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