Photodynamic therapy of hamster Greene melanoma in vitro and in vivo using bacteriochlorin-a as photosensitizer

J. J. Schuitmaker; Jaap A. Van Best; J. L. van Delft; J. E. Jannink; J. A. Oosterhuis; Gijs F.J.M. Vrensen; Didi Ms Wolff-Rouendaal; T. M.A.R. Dubbelman

doi:10.1117/12.231009

31 January 1996 Photodynamic therapy of hamster Greene melanoma in vitro and in vivo using bacteriochlorin-a as photosensitizer

J. J. Schuitmaker, Jaap A. Van Best, J. L. van Delft, J. E. Jannink, J. A. Oosterhuis, Gijs F.J.M. Vrensen, Didi Ms Wolff-Rouendaal, T. M.A.R. Dubbelman

Author Affiliations +

Proceedings Volume 2625, Photochemotherapy: Photodynamic Therapy and Other Modalities; (1996) https://doi.org/10.1117/12.231009
Event: BiOS Europe '95, 1995, Barcelona, Spain

Abstract

Efficient photodynamic therapy (PDT) of malignant melanoma may be possible with photosensitizers having absorption maxima in the far-red region e.g., above 700 nm. Bacteriochlorin a (BCA), a non toxic derivative of bacteriochlorphyllin a, has a high molecular absorption coefficient (32.000 M^-1.cm^-1) at 760 nm. At this wavelength tissue penetration of light is almost optimal and melanin absorption is relatively low. In several series of experiments BCA was proven to be a very effective photosensitizer, in vitro and in vivo. It is preferentially retained in experimental hamster Greene melanoma, rhabdomyosarcoma, RIF- and mamma tumors. Its fluorescence can be detected in vivo, thus enabling early tumor detection and it is rapidly cleared from the tissues which promises no, or minor skin photosensitivity. The effects of BCA-PDT were studied in vitro and in vivo using the heavily pigmented Hamster Greene Melanoma (HGM) cell line as a model. In vitro it was found that the uptake of BCA was time, concentration and temperature dependant. Upon illumination (10 Mw/cm², 756 nm) after incubation with 2.5 (mu) g/ml BCA for 1 h, almost complete cell kill was obtained within seconds. Hamster Greene Melanoma implanted in the anterior eye chamber of rabbits is an accepted in vivo model for ocular melanoma. The effects of BCA-PDT using this model were studied by light- and electron microscopy. Immediately after PDT intracellular spaces were enlarged and blood vessels were clotted with swollen erythrocytes. Electron microscopy showed fused inner and outer membranes and affected cristae mitchondriales of some mitochondria. With time, the severity of tissue and cell damage increased. One day after irradiation tumor growth had stopped; fluorescein angiography showed non perfusion of the tumor. Histopathology showed almost complete tumor necrosis with occasionally viable cells at the tumor periphery. It is concluded that the direct mitochondrial damage and the vascular damage both contribute to BCA-PDT induced tumor necrosis.

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J. J. Schuitmaker, Jaap A. Van Best, J. L. van Delft, J. E. Jannink, J. A. Oosterhuis, Gijs F.J.M. Vrensen, Didi Ms Wolff-Rouendaal, and T. M.A.R. Dubbelman "Photodynamic therapy of hamster Greene melanoma in vitro and in vivo using bacteriochlorin-a as photosensitizer", Proc. SPIE 2625, Photochemotherapy: Photodynamic Therapy and Other Modalities, (31 January 1996); https://doi.org/10.1117/12.231009

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